(-)-羟基柠檬酸[Hydroxycitric acid，(-)-HCA]是一种主要存在于藤黄果实外壳中的天然有机酸，因具有抑制哺乳动物脂肪合成、降低胆固醇含量、减轻炎症反应、抗氧化和增加能量消耗等多种潜在生物学功能而备受关注，但其发挥多种生物学效应的机制并不清楚。本实验室前期在家禽上的研究表明，(-)-HCA通过影响家禽脂肪代谢相关因子的表达而抑制腹部脂肪的沉积；且在胚胎期肉鸡上研究发现，(-)-HCA抑制家禽脂肪沉积的机制可能与其影响机体的糖代谢有关，但其具体的生物化学机制尚不清楚。因此，本研究以罗氏308肉鸡和鸡胚原代肝细胞为研究对象，在探讨(-)-HCA对家禽糖、脂肪及能量代谢影响的基础之上，利用Labfree技术明确(-)-HCA调节鸡胚原代肝细胞糖、脂肪和能量代谢的关键效应因子及其涉及的主要代谢途径，并进一步以油酸诱导的鸡胚原代肝细胞代谢紊乱模型深入阐明(-)-HCA调控家禽代谢稳态的确切生物化学机制。研究旨在为天然安全的代谢中间体类似物--(-)-HCA生理学功能的研究及其在畜禽生产中的应用提供一定的科学依据和理论基础。

1 (-)-羟基柠檬酸对肉鸡糖和脂肪代谢的影响及其生物化学机制

      为探讨(-)-HCA对罗氏308肉鸡葡萄糖和脂肪代谢的影响及其机制，120羽21日龄罗氏308肉鸡被随机分为对照组和日粮中添加1000 mg/kg（低）、2000 mg/kg（中）、3000 mg/kg（高）(-)-HCA处理组，每个处理组设3个重复，每个重复10羽。饲喂至49日龄，取血清和肝脏样本、待测。比色法检测糖原、甘油三酯（TG）、血糖含量以及葡萄糖分解代谢关键酶磷酸果糖激酶1（PFK-1）、丙酮酸脱氢酶（PDH）、琥珀酸脱氢酶（SDH）和苹果酸脱氢酶（MDH）活性；实时荧光定量PCR法检测脂联素受体（AdipoR）、脂肪酸合成相关因子ATP-柠檬酸裂解酶（ACLY）、乙酰辅酶A羧化酶（ACC）、脂肪酸合成酶（FAS）以及糖原合成酶（GS）和糖原磷酸化酶（GP）mRNA表达水平；Western blot分析脂肪酸合成相关因子（ACCα、p-ACCα、FAS）、葡萄糖分解代谢相关因子（PFKL、PDH、SDHA和Complex IV）以及AMP-依赖性蛋白激酶（AMPKα）、p-AMPKα、过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）、核呼吸因子1（NRF-1）和线粒体转录因子A（TFAM）蛋白表达水平。结果显示，(-)-HCA处理通过降低FAS蛋白表达水平及提高p-ACCα/ACCα表达水平，降低了肉鸡肝脏中脂滴堆积和TG含量；同时，(-)-HCA处理显著提高PFK-1、PDH、SDH和MDH的活性，进而加速肉鸡的葡萄糖分解代谢；此外，(-)-HCA处理提高了肉鸡肝脏中AdipoR1 mRNA表达水平及p-AMPKα/AMPKα、PGC-1α、NRF-1和TFAM蛋白表达水平。结果提示，日粮中添加(-)-HCA处理可通过激活AMPK信号通路加速能量代谢，最终导致肉鸡机体葡萄糖分解增强、脂肪沉积减少。

2 (-)-羟基柠檬酸对鸡胚原代肝细胞糖、脂肪和能量代谢的影响

      本部分试验在分离、培养鸡胚原代肝细胞的基础之上，探讨(-)-HCA对鸡胚原代肝细胞糖、脂肪和能量代谢关键因子表达的影响及机制。选用终浓度为0、1、10和50 μmol·L-1 (-)-HCA处理鸡胚原代肝细胞1、3、6、12或24 h后，收集细胞或上清液。以MTT和乳酸脱氢酶释放法分别检测细胞活力和死亡率；比色法检测糖原含量、TG含量、葡萄糖消耗量、SDH和MDH活性；实时荧光定量PCR法检测ACLY、ACC、FAS、固醇调节元件结合蛋白1c（SREBP-1c）、肉碱脂酰转移酶I（CPT-I）、过氧化物酶体增殖物激活受体α（PPARα）mRNA表达水平；酶联免疫吸附法（ELISA）检测葡萄糖激酶（GK）、PFK-1、丙酮酸激酶（PK）、PDH、柠檬酸合酶（CS）、乌头酸酶（ACO）、GS、GP、磷酸烯醇式丙酮酸羧激酶（PEPCK）、ACLY、NADH脱氢酶、ATP合酶及乙酰辅酶A的蛋白含量。结果显示，(-)-HCA处理通过降低脂肪酸合成相关因子ACLY、FAS和SREBP-1c mRNA表达水平及增加脂肪酸分解相关因子PPARα mRNA表达水平，抑制了鸡胚原代肝细胞中甘油三酯的沉积；同时，(-)-HCA处理降低了鸡胚原代肝细胞ACLY的活性和胞质中乙酰辅酶A含量，但明显增加鸡胚原代肝细胞葡萄糖消耗量；此外，(-)-HCA处理通过增加GK、PFK-1、PK、PDH、CS、ACO、SDH、MDH、NADH脱氢酶和ATP合酶的活性或蛋白含量，加速葡萄糖的分解代谢及能量代谢水平。结果提示，(-)-HCA通过抑制鸡胚原代肝细胞中ACLY活性和增强氧化磷化酸水平来减少胞质中脂肪酸合成的前体--乙酰辅酶A的供应，最终抑制了鸡胚原代肝细胞中脂肪的堆积。

3 (-)-羟基柠檬酸调控鸡胚原代肝细胞糖、脂肪和能量代谢的信号转导机制研究

      本部分试验以AMPK通路关键因子抑制剂或RNA干扰技术处理鸡胚原代肝细胞，以探讨(-)-HCA调控家禽糖、脂肪和能量代谢的确切信号转导机制。选用终浓度为0、1、10和50 μmol·L-1的(-)-HCA处理鸡胚原代肝细胞24 h，或以AMPK通路关键因子的激抑制剂以及利用干扰载体预处理鸡胚原代肝细胞后，添加0或10 μmol·L-1 (-)-HCA继续处理24 h，收集细胞、待测。比色法检测TG含量和葡萄糖消耗量；Western blot法检测ACCα、p-ACCα、FAS和SREBP-1等脂肪酸合成代谢以及PFKL、PDH、SDH、Complex IV、AMPKα、p-AMPKα、PGC-1α和NRF-1等糖代谢和能量代谢关键蛋白的表达水平。结果显示，(-)-HCA处理通过降低FAS和SREBP-1的蛋白表达水平及提高p-ACCα/ACCα表达水平，降低了鸡胚原代肝细胞中甘油三酯的含量；同时，(-)-HCA处理显著提高了PFK-1、PDH、SDHA和Complex IV的蛋白表达水平，从而促进了肝细胞对葡萄糖摄取和分解代谢；此外，(-)-HCA主要通过激活AMPK-PGC-1α-NRF-1信号通路来调控鸡胚原代肝细胞中脂肪和糖代谢关键因子的表达。以上结果提示，(-)-HCA通过激活AMPK-PGC-1α-NRF-1信号通路增强葡萄糖的氧化分解和氧化磷酸化水平，进而加速乙酰辅酶A彻底氧化分解以抑制脂肪酸的合成。

4 (-)-羟基柠檬酸调控鸡胚原代肝细胞糖、脂肪和能量代谢的效应蛋白筛选

      本部分试验利用蛋白质组学筛选(-)-HCA处理后鸡胚原代肝细胞中蛋白因子表达谱的变化，并利用生物信息学方法明确(-)-HCA调控鸡胚原代肝细胞糖、脂肪和能量代谢关键效应因子及其主要代谢途径。结果发现，10 μmol·L-1 (-)-HCA处理鸡胚原代肝细胞24 h后，共筛选出45个核心差异表达蛋白。生物信息学分析结果表明，核心差异表达蛋白主要涉及促进脂肪的分解及转运（APOA1、APOA4、APOB等蛋白表达上调），增加肝细胞对葡萄糖的摄取、糖酵解和氧化磷酸化（SLC2A2、ATP1A1和ATP6V0C等蛋白表达上调，PDK1、ALDH8A1等蛋白表达下调），增强肝细胞的免疫机能（TF、UBB等蛋白表达上调），调节肝细胞蛋白降解过程（CUL1、CUL3、CUL4B、CUL5等蛋白表达上调，UBE2N、PSMC1等表达下调），参与调节mRNA合成与出核（CDC42、SEH1L等表达上调，UBE2N、COPS5表达下调）等主要生物学过程，以及调控机体糖脂代谢的关键信号因子PKA亚基（PRKACB、PRKAR2A表达上调）的蛋白表达水平。结果提示，(-)-HCA主要通过调节关键效应因子的mRNA合成以及蛋白质修饰而影响鸡胚原代肝细胞中糖、脂肪和能量代谢以及蛋白质的合成与降解、免疫机能等生物学效应，且其对糖、脂肪和能量代谢的调节可能与PKA相关的关键因子的活化有关。

5 (-)-羟基柠檬酸对油酸诱导鸡胚原代肝细胞代谢紊乱的调节效应及其信号转导机制研究

      本部分试验以油酸（OA）诱导的鸡胚原代肝细胞脂代谢紊乱模型为研究对象，旨在进一步探讨(-)-HCA在调控机体代谢稳态进而缓解炎症反应的效应及其机制。鸡胚原代肝细胞在终浓度为0或10 μmol·L-1 (-)-HCA处理4 h后添加0.6 mmol·L-1 OA继续孵育24 h；同时，以AMPK通路关键因子激抑制剂或利用RNA干扰载体预处理鸡胚原代肝细胞后，以0或10 μmol·L-1 (-)-HCA处理4 h后添加0.6 mmol·L-1 OA继续孵育24 h，收集细胞、待测。油红O和尼罗红染色检测脂滴堆积状况；比色法检测丙二醛（MDA）和TG含量；流式细胞术检测活性氧（ROS）含量、凋亡率和线粒体膜电位；实时荧光定量PCR法检测炎症及凋亡相关因子mRNA表达水平；Western blot法检测脂代谢、凋亡、炎症及通路相关因子的蛋白表达水平。结果发现，(-)-HCA通过激活AMPK信号降低脂肪酸合成代谢因子FAS、SREBP-1的蛋白表达，同时增加脂肪酸分解代谢因子CPT1A、烯脂酰辅酶A水合酶1（ECHS1）等蛋白表达而抑制OA诱导下鸡胚原代肝细胞中脂滴堆积，缓解鸡胚肝细胞的脂代谢紊乱。同时，(-)-HCA通过激活AMPK-PGC-1α-NRF-1-TFAM信号通路降低OA诱导的鸡胚原代肝细胞中ROS过度堆积，从而缓解鸡胚原代肝细胞中因脂肪代谢紊乱导致的线粒体功能障碍。(-)-HCA通过降低促凋亡因子Bax、Caspase 3、Caspase 9及细胞质中Cytochrome c的表达，增加抗凋亡因子Bcl-2的表达及线粒体膜电位，从而抑制OA诱导的鸡胚原代肝细胞氧化损伤；此外，(-)-HCA阻止OA诱导的鸡胚原代肝细胞中NF-κB的核移位，进而降低炎症因子iNOS和COX-2的释放而减轻脂代谢紊乱诱导的炎症反应，且该效应与(-)-HCA抑制ROS介导的p38 MAPK信号通路活化有关。结果提示，(-)-HCA通过活化AMPK-PGC-1α-NRF-1通路缓解OA诱导的鸡胚原代肝细胞脂代谢紊乱及线粒体功能障碍；且其可通过降低ROS过度产生抑制p38 MAPK信号通路的活化而实现抗氧化损伤和抗炎效应。

      (-)-Hydroxycitric acid [(-)-HCA] is a main natural organic acid in the rind of the fruit Garcinia cambogia, and exhibits many potential biological functions, such as inhibiting fat synthesis, reducing cholesterol content, attenuating inflammation, anti-oxidation and increasing energy consumption in mammals. However, the mechanism of its biological effects is still clear. Previous studies in poultry in our laboratory showed that (-)-HCA inhibited the deposition of abdominal fat by affecting the expression of fat metabolism related factors in poultry; and studies in embryonic broilers illustrated that the mechanism of (-)-HCA inhibiting the deposition of poultry fat may be related to its effect on glucose metabolism in the body, but the specific biochemical mechanism is not clear. Therefore, Ross 308 broiler and primary chicken hepatocytes were chosen as the research object in this study. On the basis of discussing the effect of (-)-HCA on the metabolism of glucose, fat and energy in poultry, labfree technology were used to clarify the key effect factors of (-)-HCA regulating the metabolism of glucose, fat and energy in primary chicken hepatocytes and the main metabolic pathway involved, and the metabolic disorder model of primary chicken hepatocytes induced by oleic acid (OA) was used to further elucidate the exact biochemical mechanism of (-)-HCA regulating the metabolic homeostasis of poultry. The purpose of this study is to provide scientific basis and theoretical basis for the study of physiological function of natural and safe metabolic intermediate (-)-HCA and its application in livestock and poultry production.

1 Effects of (-)-hydroxycitric acid on the glucose and fat metabolism in broilers and its biochemical mechanism

      To investigate the regulation and mechanism of (-)-HCA on glucose and fat metabolism in Ross 308 broilers. 21-day-old Ross 308 broilers were randomly divided into control group and diet supplemented with 1000 mg/kg (low), 2000 mg/kg (medium), 3000 mg/kg (high) (-)-HCA treatment group (three duplicates of ten broilers per group). After feeding to 49 d, serum and liver samples were taken and tested. The contents of glycogen, triglyceride (TG), blood glucose and the activities of phosphofructokinase-1 (PFK-1), pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) were measured by colorimetry; the mRNA expression of adiponectin receptor (AdipoR), ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS), glycogen synthetase (GS) and glycogen phosphorylase (GP) were detected by quantitative real-time PCR; the protein expression of fatty acid synthesis related factors (ACCα, p-ACCα, FAS), glucose catabolism related factors (PFKL, PDH, SDHA and complex IV), AMP-dependent protein kinase (AMPKα), p-AMPKα, peroxisome proliferator activated receptor γ coactivator 1 α (PGC-1 α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) were analyzed by Western blot. The current results showed that (-)-HCA decreased the accumulation of lipid droplets and TG content by reducing fatty acid synthase protein level and enhancing phosphorylation of acetyl-CoA carboxylase protein level. (-)-HCA accelerated carbohydrate aerobic metabolisms by increasing the activities of phosphofructokinase-1, pyruvate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase. Furthermore, (-)-HCA increased AdipoR1 mRNA level and enhanced phospho-AMPKα, peroxisome proliferator-activated receptor gamma coactivator-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A protein levels in broiler chickens. These results suggested that (-)-HCA treatment could accelerate energy metabolism by activating the AMPK signal pathway, and ultimately lead to the increasing of glucose decomposition and the decreasing of fat accumulation in broilers.

2 Effects of (-)-hydroxycitric acid on the metabolism of glucose, fat and energy in primary chicken hepatocytes

      Based on the isolation and culture of primary chicken hepatocytes, the present study was designed to investigate the effects of (-)-HCA on glcucose, lipid and energy metabolism related factors and its mechanism in primary chicken hepatocytes. The primary chicken hepatocytes were treated with 0, 1, 10 and 50 μmol·L-1 (-)-HCA for 1, 3, 6, 12 or 24 h, then the cells or supernatant were collected. The cell viability and death rate were detected by MTT and LDH assay, respectively; the glycogen and TG content, glucose consumption, and the activities of SDH and MDH were measured by colorimetry; the mRNA expression of ACLY, ACC, FAS, sterol regulatory element binding protein 1c (SREBP-1c), carnitine palmitoyl transferase I (CPT-I) and peroxisome proliferator activated receptor α (PPARα) were detected by quantitative real-time PCR; the protein contents of glucose kinase (GK), PFK-1, pyruvate kinase (PK), PDH, citrate synthetase (CS), aconitase (ACO), GS, GP, phosphoenolpyruvate carboxykinase (PEPCK), ACLY, NADH dehydrogenase, ATP synthetase and acetyl-CoA were detected by ELISA. In this study, (-)-HCA treatment significantly decreased ACLY, FAS and SREBP-1c mRNA levels and markedly increased PPARα mRNA level, resulting in the inhibition of TG content. Meanwhile, (-)-HCA treatment significantly decreased ACLY activity and acetyl-CoA content in cytosol, but significantly increased glucose consumption. In addition, (-)-HCA treatment promoted the activities/contents of GK, PFK-1, PK, PDH, CS, ACO, SDH, MDH, NADH dehydrogenase and ATP synthase remarkably. These results suggested that (-)-HCA reduced the supply of acetyl-CoA, the precursor of fatty acid synthesis in the cytoplasm, which mainly achieved via inhibiting the ACLY and enhancing oxidative phosphorylation level, and finally inhibited the accumulation of fat in primary chicken hepatocytes.

3 Study on the signaling transduction mechanisms of (-)-hydroxycitric acid regulating the metabolism of glucose, fat and energy in primary chicken hepatocytes

      In this study, the AMPK pathway key factor inhibitor or RNA interference technology were used to explore the exact signal transduction mechanism of (-)-HCA regulating glucose, fat and energy metabolism in primary chicken hepatocytes. The primary chicken hepatocytes were treated with 0, 1, 10 and 50 μmol·L-1 (-)-HCA for 24 h or pretreated with the indicated activator, inhibitor or interference vector of AMPK pathway, and then treated with 0 or 10 μmol·L-1 (-)-HCA for 24 h to collect the cells and tested. Triglyceride (TG) content and glucose consumption were measured by colorimetry; the protein expression of fatty acids synthesis metabolism such as ACCα, p-ACCα, FAS and SREBP-1, the expression of glucose and energy metabolism key proteins such as PFKL, PDH, SDH, Complex IV, AMPKα, p-AMPKα, PGC-1α and NRF-1 were detected by Western blot. The results showed that (-)-HCA obviously decreased TG content through inhibiting FAS protein level, and enhancing the protein level of p-ACCα/ACCα in hepatocytes. Meanwhile, (-)-HCA markedly enhanced the protein level of PFK-1, PDH, SDHA and Complex IV, and which led to the enhancing of glucose uptake and catabolism in hepatocytes. In addition, the regulation of (-)-HCA on these key factors associated with lipid and glucose metabolism in hepatocytes was mainly achieved through activation of AMPK-PGC-1α-NRF-1 signaling pathway. These results suggested that (-)-HCA enhanced the oxidative decomposition and oxidative phosphorylation of glucose by activation of AMPK-PGC-1α-NRF-1 signaling pathway, and then accelerated the complete oxidation decomposition of acetyl-CoA to inhibit the synthesis of fatty acids.

4 Screening of effector proteins of (-)-hydroxycitric acid regulating the metabolism of glucose, fat and energy in primary chicken hepatocytes

      In this study, proteomics was used to screen the expression profile of protein factors after (-)-HCA treatment, and bioinformatics was used to determine the key effect factors and main metabolic pathways of (-)-HCA on the regulation of glucose, fat and energy metabolism in primary chicken hepatocytes. The results showed that core differentially expressed proteins were screened out after 10 μmol·L-1 (-)-HCA treatment in primary chicken hepatocytes. Bioinformatics analysis showed that core differentially expressed proteins were mainly involved in promoting the decomposition and transportion of fat (up-regulated expression of ApoA1, APOA4 and APOB), increasing the uptake of glucose, glycolysis and oxidative phosphorylation of hepatocytes (up-regulated expression of SLC2A2, ATP1A1 and ATP6V0C, down-regulated expression of PDK1, ALDH8A1, etc.), enhancing the immune function of hepatocytes (up-regulated expression of TF, UBB, etc.), regulating the degradation of hepatocyte proteins (up-regulated expression of CUL1, CUL3, CUL4B, CUL5, down-regulated expression of UBE2N, PSMC1, etc.), participating in the main biological processes such as mRNA synthesis and nucleation (up-regulated expression of CDC42, SEH1L, down-regulated expression of UBE2N, COPS5), as well as regulating the protein expression of glycolipid metabolism key signal factor PKA subunit (up-regulated expression of PRKACB and PRKAR2A). These results suggested that (-)-HCA mainly affected the biological effects of glucose, fat and energy metabolism, protein synthesis and degradation, immune function in primary chicken hepatocytes by regulating the mRNA synthesis and protein modification of key effectors, and its regulation of glucose, fat and energy metabolism might be related to the activation of key factors related to PKA.

5 Study on the regulation of (-)-hydroxycitric acid on oleic acid-induced metabolism disorder and its signaling transduction mechanisms in primary chicken hepatocytes

      In this study, the lipid metabolism disorder model of primary chicken hepatocytes induced by oleic acid (OA) was taken as the research object, in order to further explore the regulation and mechanism of (-)-HCA on the metabolism of homeostasis and inflammation. The primary chicken hepatocytes were treated with 0 or 10 μmol·L-1 (-)-HCA for 4 h and then incubated with 0.6 mmol·L-1 OA for 24 h; meanwhile, the primary chicken hepatocytes were pretreated with the key factor activator, inhibitor or RNA interference vector of AMPK pathway, then treated with 0 or 10 μmol·L-1 (-)-HCA for 4 h and then added with 0.6 mmol·L-1 OA for another 24 h, the cells were collected and tested. Oil red O and Nile red staining were used to detect lipid droplet accumulation; the malondialdehyde (MDA) and TG levels were detected by colorimetry; cellular reactive oxygen species (ROS) content, cell apoptosis rate and mitochondrial membrane potential were detected by flow cytometry; the mRNA expression of inflammation and apoptosis related factors were detected by quantitative real-time PCR; Western blot was used to detect the protein expression of lipid metabolism, apoptosis, inflammation and pathways. The results showed that (-)-HCA reduced FAS and SREBP-1 protein expression, and increased the protein expression of CPT-I, enoyl COA hydratase 1 (ECHS1) by activating AMPK signaling, then inhibited OA-induced accumulation of lipid droplets and alleviated lipid metabolism disorder of primary chicken hepatocytes. Meanwhile, (-)-HCA reduced OA-induced excessive accumulation of ROS and alleviated mitochondrial dysfunction caused by fat metabolism disorder through the activation of AMPK-PGC-1α-NRF-1-TFAM signaling pathway in primary chicken hepatocytes. (-)-HCA reduced the expression of apoptogenic factor Bax, caspase 3, caspase-9 and cytochrome c, and increased anti-apoptotic factor Bcl-2 expression and mitochondrial membrane potential, eventually inhibiting OA-induced oxidative damage in primary chicken hepatocytes. In addition, (-)-HCA prevented the nuclear translocation of NF-κB in primary chicken hepatocytes induced by OA, reduced the release of iNOS and COX-2, and finally reduced the inflammatory effect caused by lipid metabolism disorder, which was related to the inhibition of ROS mediated the activation of p38 MAPK signaling pathway. These results suggested that (-)-HCA alleviated lipid metabolism disorder and mitochondrial dysfunction of OA-induced primary hepatocytes by activating AMPK-PGC-1α-NRF-1 pathway, and subsequently achieved anti-oxidation and anti-inflammatory effect by reducing ROS overproduction and inhibiting the activation of p38 MAPK signaling pathway.

[1] Gyamfi D and Danquah K O. Chapter 1 - Nutrients and Liver Metabolism[M]. Molecular Aspects of Alcohol & Nutrition, 2016: 3-15.

[2] Hazelwood R L and Lorenz F W. Effects of fasting and insulin on carbohydrate metabolism of the domestic fowl[J]. American Journal of Physiology, 1959, 197(1): 47-51.

[3] Braun E J and Sweazea K L. Glucose regulation in birds[J]. Comparative Biochemistry and Physiology B-Biochemistry & Molecular Biology, 2008, 151(1): 1-9.

[4] Dupont J, Dagou C, Derouet M, et al. Early steps of insulin receptor signaling in chicken and rat: apparent refractoriness in chicken muscle[J]. Domestic Animal Endocrinology, 2004, 26(2): 127-142.

[5] Dudas P L, Pelis R M, Braun E J, et al. Transepithelial urate transport by avian renal proximal tubule epithelium in primary culture[J]. Journal of Experimental Biology, 2005, 208(Pt 22): 4305-4315.

[6] Choshniak I, Munck B G and Skadhauge E. Sodium chloride transport across the chicken coprodeum. Basic characteristics and dependence on sodium chloride intake[J]. Journal of Physiology, 1977, 271(2): 489-503.

[7] Lind J, Munck B G, Olsen O, et al. Effects of sugars, amino acids and inhibitors on electrolyte transport across hen colon at different sodium chloride intakes[J]. Journal of Physiology, 1980, 305: 315-325.

[8] Karasov W H and Cork S J. Glucose absorption by a nectarivorous bird: the passive pathway is paramount[J]. American Journal of Physiology, 1994, 267(1 Pt 1): G18-26.

[9] Wang M Y, Tsai M Y and Wang C. Identification of chicken liver glucose transporter[J]. Archives of Biochemistry and Biophysics, 1994, 310(1): 172-179.

[10] Kono T, Nishida M, Nishiki Y, et al. Characterisation of glucose transporter (GLUT) gene expression in broiler chickens[J]. British Poultry Science, 2005, 46(4): 510-515.

[11] Jones J G. Hepatic glucose and lipid metabolism[J]. Diabetologia, 2016, 59(6): 1098-1103.

[12] Panserat S, Rideau N and Polakof S. Nutritional regulation of glucokinase: A cross-species story[J]. Nutrition Research Reviews, 2014, 27(1): 21-47.

[13] Espinet C, Bartrons R and Carreras J. Effects of fructose 2, 6-bisphosphate and glucose 1, 6-bisphosphate on phosphofructokinase from chicken erythrocytes[J]. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 1988, 90(2): 453-457.

[14] Espinet C, Bartrons R and Carreras J. Fructose 2, 6-bisphosphate and glucose 1, 6-bisphosphate in erythrocytes during chicken development[J]. FEBS Letters, 1986, 209(2): 254-256.

[15] Lang L, Chemmalakuzhy R, Shay C, et al. PFKP signaling at a glance: An emerging mediator of cancer cell metabolism[J]. Advances in Experimental Medicine and Biology, 2019, 1134: 243-258.

[16] Lonberg N and Gilbert W. Primary structure of chicken muscle pyruvate kinase mRNA[J]. Proceedings of the National Academy of Sciences of the United States of America, 1983, 80(12): 3661-3665.

[17] Israelsen W J and Vander Heiden M G. Pyruvate kinase: Function, regulation and role in cancer[J]. Seminars in Cell & Developmental Biology, 2015, 43: 43-51.

[18] 邓述欢, 高玲. 血清丙酮酸激酶与血糖关系的探讨[J]. 现代检验医学杂志, 2001, 16(1): 59.

Deng S H, Gao L. Study on the relationship between serum pyruvate kinase and blood glucose [J]. Journal of Modern Laboratory Medicine, 2001, 16(1): 59 (in Chinese).

[19] Rasheed M R H A and Tarjan G. Succinate dehydrogenase complex: An updated review[J]. Archives of Pathology & Laboratory Medicine, 2018, 142(12): 1564-1570.

[20] Bersch K, Lobos Matthei I and Thoms S. Multiple localization by functional translational readthrough[J]. Subcell Biochem, 2018, 89: 201-219.

[21] Wang Y, Zhu Q, Yang L, et al. Ontogenic expression pattern and genetic polymorphisms of the fatty acid transport protein 4 (FATP4) gene in chinese chicken populations[J]. International Journal of Molecular Sciences, 2012, 13(6): 6820-6835.

[22] Burke A C and Huff M W. ATP-citrate lyase: genetics, molecular biology and therapeutic target for dyslipidemia[J]. Current Opinion in Lipidology, 2017, 28(2): 193-200.

[23] Bazilevsky G A, Affronti H C, Wei X, et al. ATP-citrate lyase multimerization is required for coenzyme-A substrate binding and catalysis[J]. Journal of Biological Chemistry, 2019, 294(18): 7259-7268.

[24] Wellen K E, Hatzivassiliou G, Sachdeva U M, et al. ATP-citrate lyase links cellular metabolism to histone acetylation[J]. Science, 2009, 324(5930): 1076-1080.

[25] Beigneux A P, Kosinski C, Gavino B, et al. ATP-citrate lyase deficiency in the mouse[J]. Journal of Biological Chemistry, 2004, 279(10): 9557-9564.

[26] Elshourbagy N A, Near J C, Kmetz P J, et al. Rat ATP citrate-lyase. Molecular cloning and sequence analysis of a full-length cDNA and mRNA abundance as a function of diet, organ, and age[J]. Journal of Biological Chemistry, 1990, 265(3): 1430-1435.

[27] Chu K Y, Lin Y L, Hendel A, et al. ATP-citrate lyase reduction mediates palmitate-induced apoptosis in pancreatic beta cells[J]. Journal of Biological Chemistry. 2010, 285(42):32606-32615.

[28] Sato R, Okamoto A, Inoue J, et al. Transcriptional regulation of the ATP citrate-lyase gene by sterol regulatory element-binding proteins[J]. Journal of Biological Chemistry, 2000, 275(17): 12497-12502.

[29] Potapova I A, El-Maghrabi M R, Doronin S V, et al. Phosphorylation of recombinant human ATP:citrate lyase by cAMP-dependent protein kinase abolishes homotropic allosteric regulation of the enzyme by citrate and increases the enzyme activity. Allosteric activation of ATP: citrate lyase by phosphorylated sugars[J]. Biochemistry, 2000, 39(5): 1169-1179.

[30] Lee J V, Carrer A, Shah S, et al. Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation[J]. Cell Metabolism, 2014, 20(2): 306-319.

[31] Covarrubias A J, Aksoylar H I, Yu J, et al. Akt-mTORC1 signaling regulates acly to integrate metabolic input to control of macrophage activation[J]. Elife, 2016, 5: e11612.

[32] Osinalde N, Mitxelena J, Sanchez-Quiles V, et al. Nuclear phosphoproteomic screen uncovers ACLY as mediator of IL-2-induced proliferation of CD4+ T lymphocytes[J]. Molecular & Cellular Proteomics, 2016, 15(6): 2076-2092.

[33] Xin M, Qiao Z G, Li J, et al. miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer[J]. Oncotarget, 2016, 7(28): 44252-44265.

[34] Wang M N, Li L L, Liu R, et al. Obesity-induced overexpression of miRNA-24 regulates cholesterol uptake and lipid metabolism by targeting SR-B1[J]. Gene, 2018, 668: 196-203.

[35] Brownsey R W, Boone A N, Elliott J E, et al. Regulation of acetyl-CoA carboxylase[J]. Biochemical Society Transactions, 2006, 34: 223-227.

[36] Barber M C, Price N T and Travers M T. Structure and regulation of acetyl-CoA carboxylase genes of metazoa[J]. Biochimica et Biophysica Acta, 2005, 1733(1): 1-28.

[37] Chen L Y, Duan Y Q, Wei H Q, et al. Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1/2 inhibitors[J]. Expert Opinion on Investigational Drugs, 2019, 28(10): 917-930.

[38] Meegalla R L, Billheimer J T and Cheng D. Concerted elevation of acyl-Coenzyme A:diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin[J]. Biochemical and Biophysical Research Communications, 2002, 298(3): 317-323.

[39] Yahagi N, Shimano H, Hasegawa K, et al. Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma[J]. European Journal of Cancer, 2005, 41(9): 1316-1322.

[40] Donaldson W E. Biotin effects on fatty acid synthesis in chicks[J]. Annals of the New York Academy of Sciences, 1985, 447: 105-111.

[41] Iritani N. Nutritional and hormonal regulation of lipogenic-enzyme gene expression in rat liver[J]. European Journal of Biochemistry, 1992, 205(2): 433-442.

[42] Smith S. The animal fatty acid synthase: one gene, one polypeptide, seven enzymes[J]. FASEB Journal, 1994, 8(15): 1248-1259.

[43] Che L, Paliogiannis P, Cigliano A, et al. Pathogenetic, prognostic, and therapeutic role of fatty acid synthase in human hepatocellular carcinoma[J]. Frontiers in Oncology, 2019, 9: 1412.

[44] 田维熙. 动物的体脂水平和脂肪酸合成酶活性的调控[J]. 生命的化学, 1994, 1: 1-2.

Tian W X. Regulation of body fat level and fatty acid synthetase activity in animals[J]. Chemistry of Life, 1994, 1: 1-2 (in Chinese).

[45] Paulauskis J D and Sul H S. Cloning and expression of mouse fatty acid synthase and other specific mRNAs. Developmental and hormonal regulation in 3T3-L1 cells[J]. Journal of Biological Chemistry, 1988, 263(15): 7049-7054.

[46] Back D W, Goldman M J, Fisch J E, et al. The fatty acid synthase gene in avian liver. Two mRNAs are expressed and regulated in parallel by feeding, primarily at the level of transcription[J]. Journal of Biological Chemistry, 1986, 261(9): 4190-4197.

[47] Goodridge A G, Crish J F, Hillgartner F B, et al. Nutritional and hormonal regulation of the gene for avian malic enzyme[J]. Journal of Nutrition, 1989, 119(2): 299-308.

[48] Blake W L and Clarke S D. Suppression of rat hepatic fatty acid synthase and S14 gene transcription by dietary polyunsaturated fat[J]. Journal of Nutrition, 1990, 120(12): 1727-1729.

[49] Xu J, Cho H, O'Malley S, et al. Dietary polyunsaturated fats regulate rat liver sterol regulatory element binding proteins-1 and -2 in three distinct stages and by different mechanisms[J]. Journal of Nutrition, 2002, 132(11): 3333-3339.

[50] Yamazaki N, Yamanaka Y, Hashimoto Y, et al. Structural features of the gene encoding human muscle type carnitine palmitoyltransferase I[J]. FEBS Letters, 1997, 409(3): 401-406.

[51] Barger P M, Brandt J M, Leone T C, et al. Deactivation of peroxisome proliferator-activated receptor-α during cardiac hypertrophic growth[J]. Journal of Clinical Investigation, 2000, 105(12): 1723-1730.

[52] Shimano H and Sato R. SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology[J]. Nature Reviews Endocrinology, 2017, 13(12): 710-730.

[53] Raghow R, Dong Q M and Elam M B. Phosphorylation dependent proteostasis of sterol regulatory element binding proteins[J]. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 2019, 1864(8): 1145-1156.

[54] Engelking L J, Cantoria M J, Xu Y C, et al. Developmental and extrahepatic physiological functions of SREBP pathway genes in mice[J]. Seminars in Cell & Developmental Biology, 2018, 81: 98-109.

[55] Xu P, Zhai Y G and Wang J. The role of PPAR and its cross-talk with CAR and LXR in obesity and atherosclerosis[J]. International Journal of Molecular Sciences, 2018, 19(4): 1260.

[56] Kao Y C, Wei W Y, Tsai K J, et al. High fat diet suppresses peroxisome proliferator-activated receptors and reduces dopaminergic neurons in the substantia nigra[J]. International Journal of Molecular Sciences, 2019, 21(1): 207.

[57] Marion-Letellier R, Savoye G and Ghosh S. Fatty acids, eicosanoids and PPAR gamma[J]. European Journal of Pharmacology, 2016, 785: 44-49.

[58] Ahmadian M, Abbott M J, Tang T Y, et al. Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype[J]. Cell Metabolism, 2011, 13(6): 739-748.

[59] Marsin A S, Bertrand L, Rider M H, et al. Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia[J]. Current Biology, 2000, 10(20): 1247-1255.

[60] J?ger S, Handschin C, St-Pierre J, et al. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha[J]. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(29): 12017-12022.

[61] Ross F A, MacKintosh C and Hardie D G. AMP-activated protein kinase: a cellular energy sensor that comes in 12 flavours[J]. FEBS Journal, 2016, 283(16): 2987-3001.

[62] Stapleton D, Mitchelhill K I, Gao G, et al. Mammalian AMP-activated protein kinase subfamily[J]. Journal of Biological Chemistry, 1996, 271(2): 611-614.

[63] Cheung P C, Salt I P, Davies S P, et al. Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding[J]. Biochemical Journal, 2000, 346 Pt 3(Pt 3): 659-669.

[64] Thornton C, Snowden M A and Carling D. Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle[J]. Journal of Biological Chemistry, 1998, 273(20): 12443-12450.

[65] Proszkowiec-Weglarz M, Richards M P, Ramachandran R, et al. Characterization of the AMP-activated protein kinase pathway in chickens[J]. Comparative Biochemistry and Physiology B-Biochemistry and Molecular Biology, 2006, 143(1): 92-106.

[66] Hawley S A, Selbert M A, Goldstein E G, et al. 5'-AMP activates the AMP-activated protein kinase cascade, and Ca2+/calmodulin activates the calmodulin-dependent protein kinase I cascade, via three independent mechanisms[J]. Journal of Biological Chemistry, 1995, 270(45): 27186-27191.

[67] Davies S P, Helps N R, Cohen P T, et al. 5'-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC[J]. FEBS Letters, 1995, 377(3): 421-425.

[68] Gowans G J, Hawley S A, Ross F A, et al. AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation[J]. Cell Metabolism, 2013, 18(4): 556-566.

[69] Hardie D G, Carling D and Gamblin S J. AMP-activated protein kinase: also regulated by ADP[J]? Trends in Biochemical Sciences, 2011, 36(9): 470-477.

[70] Shaw R J, Lamia K A, Vasquez D, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin[J]. Science, 2005, 310(5754): 1642-1646.

[71] Shan T Z, Zhang P P, Bi P P, et al. Lkb1 deletion promotes ectopic lipid accumulation in muscle progenitor cells and mature muscles[J]. Journal of Cellular Physiology. 2015, 230(5):1033-1041.

[72] Shackelford D B and Shaw R J. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression[J]. Nature Reviews Cancer, 2009, 9(8): 563-575.

[73] Marcelo K L, Means A R and York B. The Ca(2+)/Calmodulin/CaMKK2 axis: Nature's metabolic caMshaft[J]. Trends in Endocrinology and Metabolism, 2016, 27(10): 706-718.

[74] Bultot L, Guigas B, Von Wilamowitz-Moellendorff A V, et al. AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase[J]. Biochemical Journal, 2012, 443(1): 193-203.

[75] Zibrova D, Vandermoere F, G?ransson O, et al. GFAT1 phosphorylation by AMPK promotes VEGF-induced angiogenesis[J]. Biochemical Journal, 2017, 474(6): 983-1001.

[76] Kim J H, Park J M, Yea K, et al. Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake[J]. PloS One, 2010, 5(3): e9600.

[77] Zhang Y and Xu H. Translational regulation of mitochondrial biogenesis[J]. Biochemical Society Transactions, 2016, 44(6): 1717-1724.

[78] Narkar V A, Downes M, Yu R T, et al. AMPK and PPARdelta agonists are exercise mimetics[J]. Cell, 2008, 134(3): 405-415.

[79] Garcia-Roves P M, Osler M E, Holmstr?m M H, et al. Gain-of-function R225Q mutation in AMP-activated protein kinase gamma3 subunit increases mitochondrial biogenesis in glycolytic skeletal muscle[J]. Journal of Biological Chemistry, 2008, 283(51): 35724-35734.

[80] Lantier L, Fentz J, Mounier R, et al. AMPK controls exercise endurance, mitochondrial oxidative capacity, and skeletal muscle integrity[J]. FASEB Journal, 2014, 28(7): 3211-3224.

[81] O'Neill H M, Maarbjerg S J, Crane J D, et al. AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise[J]. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(38): 16092-16097.

[82] Jeppesen J, Maarbjerg S J, Jordy A B, et al. LKB1 regulates lipid oxidation during exercise independently of AMPK[J]. Diabetes, 2013, 62(5): 1490-1499.

[83] Zong H H, Ren J M, Young L H, et al. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation[J]. Proceedings of the National Academy of Sciences of the United States of America, 2002, 99(25): 15983-15987.

[84] Rodgers J T, Lerin C, Haas W, et al. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1[J]. Nature, 2005, 434(7029): 113-118.

[85] Teyssier C, Ma H, Emter R, et al. Activation of nuclear receptor coactivator PGC-1alpha by arginine methylation[J]. Genes & Development, 2005, 19(12): 1466-1473.

[86] Li X H, Monks B, Ge Q Y, et al. Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator[J]. Nature, 2007, 447(7147): 1012-1016.

[87] Lin J D, Wu H, Tarr P T, et al. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres[J]. Nature, 2002, 418(6899): 797-801.

[88] Chawla A, Repa J J, Evans R M, et al. Nuclear receptors and lipid physiology: opening the X-files[J]. Science, 2001, 294(5548): 1866-1870.

[89] Puigserver P and Spiegelman B M. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator[J]. Endocrine Reviews, 2003, 24(1): 78-90.

[90] Kressler D, Schreiber S N, Knutti D, et al. The PGC-1-related protein PERC is a selective coactivator of estrogen receptor alpha[J]. Journal of Biological Chemistry, 2002, 277(16): 13918-13925.

[91] Bost F and Kaminski L. The metabolic modulator PGC-1α in cancer[J]. American Journal of Cancer Research, 2019, 9(2): 198-211.

[92] Handschin C, Rhee J, Lin J, et al. An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle[J]. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(12): 7111-7116.

[93] Herzig S, Long F, Jhala U S, et al. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1[J]. Nature, 2001, 413(6852): 179-183.

[94] Yoon J C, Puigserver P, Chen G, et al. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1[J]. Nature, 2001, 413(6852): 131-138.

[95] J?rgensen S B, Wojtaszewski J F P, Viollet B, et al. Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle[J]. FASEB Journal, 2005, 19(9): 1146-1148.

[96] Borniquel S, Valle I, Cadenas S, et al. Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC-1alpha[J]. FASEB Journal, 2006, 20(11): 1889-1891.

[97] Gerhart-Hines Z, Rodgers J T, Bare O, et al. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha[J]. EMBO Journal, 2007, 26(7): 1913-1923.

[98] Anderson R M, Barger J L, Edwards M G, et al. Dynamic regulation of PGC-1alpha localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response[J]. Aging Cell, 2008, 7(1): 101-111.

[99] Lin J D, Handschin C and Spiegelman B M. Metabolic control through the PGC-1 family of transcription coactivators[J]. Cell Metabolism, 2005, 1(6): 361-370.

[100] Shimba Y, Togawa H, Senoo N, et al. Skeletal muscle-specific PGC-1α overexpression suppresses atherosclerosis in apolipoprotein E-knockout mice[J]. Scientific Reports, 2019, 9(1): 4077.

[101] Calvo J A, Daniels T G, Wang X M, et al. Muscle-specific expression of PPARgamma coactivator-1alpha improves exercise performance and increases peak oxygen uptake[J]. Journal of Applied Physiology, 2008, 104(5): 1304-1312.

[102] Huang T Y, Zheng D H, Houmard J A, et al. Overexpression of PGC-1α increases peroxisomal activity and mitochondrial fatty acid oxidation in human primary myotubes[J]. American Journal of Physiology-Endocrinology and Metabolism, 2017, 312(4): E253-E263.

[103] Summermatter S, Baum O, Santos G, et al. Peroxisome proliferator-activated receptor {gamma} coactivator 1{alpha} (PGC-1{alpha}) promotes skeletal muscle lipid refueling in vivo by activating de novo lipogenesis and the pentose phosphate pathway[J]. Journal of Biological Chemistry, 2010, 285(43): 32793-32800.

[104] Aharoni-Simon M, Hann-Obercyger M, Pen S, et al. Fatty liver is associated with impaired activity of PPARγ-coactivator 1α (PGC1α) and mitochondrial biogenesis in mice[J]. Laboratory Investigation, 2011, 91(7): 1018-1028.

[105] Croce M A, Eagon J C, LaRiviere L L, et al. Hepatic lipin 1beta expression is diminished in insulin-resistant obese subjects and is reactivated by marked weight loss[J]. Diabetes, 2007, 56(9): 2395-2399.

[106] Morris E M, Meers G M E, Booth F W, et al. PGC-1α overexpression results in increased hepatic fatty acid oxidation with reduced triacylglycerol accumulation and secretion[J]. American journal of Physiology[J]. Gastrointestinal and Liver Physiology, 2012, 303(3): G979-G992.

[107] Picca A and Lezza A M S. Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions: Useful insights from aging and calorie restriction studies[J]. Mitochondrion, 2015, 25: 67-75.

[1] Lim S, Oh T J and Koh K K. Mechanistic link between nonalcoholic fatty liver disease and cardiometabolic disorders[J]. International Journal of Cardiology, 2015, 201: 408-414.

[2] Tseng Y J, Dong L, Liu Y F, et al. Role of autophagy in chronic liver inflammation and fibrosis[J]. Current Protein & Peptide Science, 2019, 20(8): 817-822.

[3] Krenkel O, Puengel T, Govaere O, et al. Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis[J]. Hepatology, 2018, 67(4): 1270-1283.

[4] Van Gaal L F, Mertens I L and De Block C E. Mechanisms linking obesity with cardiovascular disease[J]. Nature, 2006, 444(7121): 875-880.

[5] Visser M, Bouter L M, McQuillan G M, et al. Elevated C-reactive protein levels in overweight and obese adults[J]. JAMA, 1999, 282(22): 2131-2135.

[6] Esposito K, Pontillo A, Palo C D, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial[J]. JAMA, 2003, 289(4): 1799-1804.

[7] Ridker P M, Buring J E, Cook N R, et al. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14719 initially healthy American women[J]. Circulation, 2003, 107(3): 391-397.

[8] Dandona P, Mohanty P, Hamouda W, et al. Inhibitory effect of a two day fast on reactive oxygen species (ROS) generation by leucocytes and plasma ortho-tyrosine and meta-tyrosine concentrations[J]. Journal of Clinical Endocrinology & Metabolism, 2001, 86(6): 2899-2902.

[9] Dandona P, Kumar V, Aljada A, et al. Angiotensin II receptor blocker valsartan suppresses reactive oxygen species generation in leukocytes, nuclear factor-kappa B, in mononuclear cells of normal subjects: evidence of an antiinflammatory action[J]. Journal of Clinical Endocrinology & Metabolism, 2003, 88(9): 4496-4501.

[10] Koh K K, Han S H and Quon M J. Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions[J]. Journal of the American College of Cardiology, 2005, 46(11): 1978-1985.

[11] Paraskevas K I, Stathopoulos V and Mikhailidis D P. Pleiotropic effects of statins: implications for a wide range of diseases[J]. Current Vascular Pharmacology, 2008, 6(4): 237-239.

[12] Aljada A, Ghanim H, Friedman J, et al. Troglitazone reduces the expression of PPARgamma while stimulating that of PPARalpha in mononuclear cells in obese subjects[J]. Journal of Clinical Endocrinology & Metabolism, 2001, 86(7): 3130-3133.

[13] Staniek K and Nohl H. H2O2 detection from intact mitochondria as a measure for one-electron reduction of dioxygen requires a non-invasive assay system[J]. Biochimica et Biophysica Acta, 1999, 1413(2): 70-80.

[14] Bartoli C G, Gómez F, Martínez D E, et al. Mitochondria are the main target for oxidative damage in leaves of wheat (Triticum aestivum L.)[J]. Journal of Experimental Botany, 2004, 55(403): 1663-1669.

[15] Berry B J, Trewin A J, Amitrano A M, et al. Use the protonmotive force: Mitochondrial uncoupling and reactive oxygen species[J]. Journal of Molecular Biology, 2018, 430(21): 3873-3891.

[16] Forrester S J, Kikuchi D S, Hernandes M S, et al. Reactive oxygen species in metabolic and inflammatory signaling[J]. Circulation Research, 2018, 122(6): 877-902.

[17] Boutros T, Chevet E and Metrakos P. Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: roles in cell growth, death, and cancer[J]. Pharmacological Reviews, 2008, 60(3): 261-310.

[18] Haagenson K K and Wu G S. The role of MAP kinases and MAP kinase phosphatase-1 in resistance to breast cancer treatment[J]. Cancer Metastasis Reviews, 2010, 29(1): 143-149.

[19] Torres M and Forman H J. Redox signaling and the MAP kinase pathways[J]. Biofactors, 2003, 17(1-4): 287-296.

[20] Flores K, Yadav S S, Katz A A, et al. The nuclear translocation of mitogen-activated protein kinases: Molecular mechanisms and use as novel therapeutic target[J]. Neuroendocrinology, 2019, 108(2): 121-131.

[21] Giri H, Cai X F, Panicker S R, et al. Thrombomodulin regulation of mitogen-activated protein kinases[J]. International Journal of Molecular Sciences, 2019, 20(8): 1851.

[22] Kim E K and Choi E J. Compromised MAPK signaling in human diseases: an update[J]. Archives of Toxicology, 2015, 89(6): 867-882.

[23] Ruffels J, Griffin M and Dickenson J M. Activation of ERK1/2, JNK and PKB by hydrogen peroxide in human SH-SY5Y neuroblastoma cells: role of ERK1/2 in H2O2-induced cell death[J]. European Journal of Pharmacology, 2004, 483(2-3): 163-173.

[24] McCubrey J A, Lahair M M and Franklin R A. Reactive oxygen species-induced activation of the MAP kinase signaling pathways[J]. Antioxidants & Redox Signaling. 2006, 8(9-10):1775-1789.

[25] Meng D, Shi X L, Jiang B H, et al. Insulin-like growth factor-I (IGF-I) induces epidermal growth factor receptor transactivation and cell proliferation through reactive oxygen species[J]. Free Radical Biology and Medicine, 2007, 42(11): 1651-1660.

[26] Kamata H, Honda S I, Maeda S, et al. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases[J]. Cell, 2005, 120(5): 649-661.

[27] Hou N, Torii S, Saito N, et al. Reactive oxygen species-mediated pancreatic beta-cell death is regulated by interactions between stress-activated protein kinases, p38 and c-Jun N-terminal kinase, and mitogen-activated protein kinase phosphatases[J]. Endocrinology, 2008, 149(4): 1654-1665.

[28] Tak P P and Firestein G S. NF-kappaB: a key role in inflammatory diseases[J]. Journal of Clinical Investigation, 2001, 107(1): 7-11.

[29] Holtmann H, Winzen R, Holland P, et al. Induction of interleukin-8 synthesis integrates effects on transcription and mRNA degradation from at least three different cytokine- or stress-activated signal transduction pathways[J]. Molecular and Cellular Biology, 1999, 19(10): 6742-6753.

[30] Sun S C. The non-canonical NF-κB pathway in immunity and inflammation[J]. Nature Reviews Immunology, 2017, 17(9): 545-558.

[31] Hayden M S and Ghosh S. Shared principles in NF-kappaB signaling[J]. Cell, 2008, 132(3): 344-362.

[32] Nolan G P and Baltimore D. The inhibitory ankyrin and activator Rel proteins[J]. Current Opinion in Genetics & Development, 1992, 2(2): 211-220.

[33] Isra?l A. The IKK complex, a central regulator of NF-kappaB activation[J]. Cold Spring Harbor Perspectives in Biology, 2010, 2(3): a000158.

[34] Taniguchi K and Karin M. NF-κB, inflammation, immunity and cancer: Coming of age[J]. Nature Reviews Immunology, 2018, 18(5): 309-324.

[35] Kabe Y, Ando K, Hirao S, et al. Redox regulation of NF-kappaB activation: distinct redox regulation between the cytoplasm and the nucleus[J]. Antioxidants & Redox Signaling, 2005, 7(3-4): 395-403.

[36] Meyer M, Schreck R and Baeuerle P A. H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor[J]. EMBO Journal, 1993, 12(5): 2005-2015.

[37] Hirota K, Matsui M, Iwata S, et al. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1[J]. Proceedings of the National Academy of Sciences of the United States of America, 1997, 94(8): 3633-3638.

[38] Morgan M J and Liu Z G. Crosstalk of reactive oxygen species and NF-κB signaling[J]. Cell Research, 2011, 21(1): 103-115.

[39] Toledano M B and Leonard W J. Modulation of transcription factor NF-kappa B binding activity by oxidation-reduction in vitro[J]. Proceedings of the National Academy of Sciences of the United States of America, 1991, 88(10): 4328-4332.

[40] Toledano M B, Ghosh D, Trinh F, et al. N-terminal DNA-binding domains contribute to differential DNA-binding specificities of NF-kappa B p50 and p65[J]. Molecular and Cellular Biology, 1993, 13(2): 852-860.

[41] Matthews J R, Wakasugi N, Virelizier J L, et al. Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62[J]. Nucleic Acids Research, 1992, 20(15): 3821-3830.

[42] Matthews J R, Kaszubska W, Turcatti G, et al. Role of cysteine62 in DNA recognition by the P50 subunit of NF-kappa B[J]. Nucleic Acids Research, 1993, 21(8): 1727-1734.

[43] Hill B G and Bhatnagar A. Protein S-glutathiolation: redox-sensitive regulation of protein function[J]. Journal of Molecular and Cellular Cardiology, 2012, 52(3): 559-567.

[44] Jamaluddin M, Wang S, Boldogh I, et al. TNF-alpha-induced NF-kappaB/RelA Ser(276) phosphorylation and enhanceosome formation is mediated by an ROS-dependent PKAc pathway[J]. Cellular Signaling, 2007, 19(7): 1419-1433.

[45] Liu J, Yoshida Y and Yamashita U. DNA-binding activity of NF-kappaB and phosphorylation of p65 are induced by N-acetylcysteine through phosphatidylinositol (PI) 3-kinase[J]. Molecular Immunology, 2008, 45(15): 3984-3989.

[46] Kil I S, Kim S Y and Park J W. Glutathionylation regulates IkappaB[J]. Biochemical and Biophysical Research Communications, 2008, 373(1): 169-173.

[47] Schieven G L, Kirihara J M, Myers D E, et al. Reactive oxygen intermediates activate NF-kappa B in a tyrosine kinase-dependent mechanism and in combination with vanadate activate the p56lck and p59fyn tyrosine kinases in human lymphocytes[J]. Blood, 1993, 82(4): 1212-1220.

[48] Panopoulos A, Harraz M, Engelhardt J F, et al. Iron-mediated H2O2 production as a mechanism for cell type-specific inhibition of tumor necrosis factor alpha-induced but not interleukin-1beta-induced IkappaB kinase complex/nuclear factor-kappaB activation[J]. Journal of Biological Chemistry, 2005, 280(40): 2912-2923.

[49] Reynaert N L, van der Vliet A, Guala A S, et al. Dynamic redox control of NF-kappaB through glutaredoxin-regulated S-glutathionylation of inhibitory kappaB kinase beta[J]. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103(35): 13086-13091.

[50] Herscovitch M, Comb W, Ennis T, et al. Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347[J]. Biochemical and Biophysical Research Communications, 2008, 367(1): 103-108.

[1] Roy S, Rink C, Khanna S, et al. Body weight and abdominal fat gene expression profile in response to a novel hydroxycitric acid-based dietary supplement[J]. Gene Expression, 2004, 11(5-6): 251-262.

[2] Tharachand, Selvaraj I and Avadhani M. Medicinal properties of malabar tamarind [Garcinia cambogia (Gaertn.) DESR.][J]. International Journal of Pharmaceutical Sciences Review and Research, 2013, 19: 101-107.

[3] Jena B S, Jayaprakasha G K, Singh R P, et al. Chemistry and biochemistry of (?)-Hydroxycitric Acid from Garcinia[J]. Journal of Agricultural and Food Chemistry, 2002, 50(1): 10-22.

[4] Kuriyan K I and Pandya K C. A note on the main constituents of the dried rind of the fruit of Garcinia cambogia[J]. Journal of the Indian Chemical Society, 1931, 81: 469-469.

[5] Lewis Y S, Neelakantan S and Anjanamurthy C. Acids in Garcinia cambogia[J]. Current Science, 1964, 33: 82-83.

[6] Yamada T, Hida H and Yamada Y. Chemistry, physiological properties, and microbial production of hydroxycitric acid[J]. Applied Microbiology and Biotechnology, 2007, 75(5): 977-982.

[7] Chuah L O, Ho W Y, Beh B K, et al. Updates on antiobesity effect of Garcinia origin (-)-HCA[J]. Evidence-Based Complementary and Alternative Medicine, 2013, 2013: 751658.

[8] Márquez F, Babio N, Bulló M, et al. Evaluation of the safety and efficacy of hydroxycitric acid or Garcinia cambogia extracts in humans[J]. Critical Reviews in Food Science and Nutrition, 2012, 52(7): 585-594.

[9] Watson J A, Fang M and Lowenstein J M. Tricarballylate and hydroxycitrate: Substrate and inhibitor of ATP: Citrate oxaloacetate lyase[J]. Archives of Biochemistry and Biophysics, 1969, 135(1): 209-217.

[10] Astell K J, Mathai M L and Su X Q. A review on botanical species and chemical compounds with appetite suppressing properties for body weight control[J]. Plant Foods for Human Nutrition, 2013, 68(3): 213-221.

[11] Spencer A F and Lowenstein J M. Citrate and the conversion of carbohydrate into fat. Citrate cleavage in obesity and lactation[J]. Biochemical Journal, 1966, 99(3): 760-765.

[12] Laubner K, Kieffer T J, Ni T L, et al. Inhibition of preproinsulin gene expression by leptin induction of suppressor of cytokine signaling 3 in pancreatic beta-cells[J]. Diabetes, 2006, 54(12): 3410-3417.

[13] Hayamizu K, Hirakawa H, Oikawa D, et al. Effect of Garcinia cambogia extract on serum leptin and insulin in mice[J]. Fitoterapia, 2003, 74(3): 267-273.

[14] Beynen A C and Geelen M J. Effects of insulin and glucagon on fatty acid synthesis from acetate by hepatocytes incubated with (-)-hydroxycitrate[J]. Endokrinologie, 1982, 79(2): 308-310.

[15] Barth C, Hackenschmidt J, Ullmann H, et al. Inhibition of cholesterol synthesis by (-)-hydroxycitrate in perfused rat liver. Evidence for an extramitochondrial mevalonate synthesis from acetyl coenzyme A[J]. FEBS Letters, 1972, 22(3): 343-346.

[16] Hashimoto T and Numa S. Kinetic studies on the reaction mechanism and the citrate activation of liver acetyl coenzyme A carboxylase[J]. European Journal of Biochemistry, 1971, 18(3): 319-331.

[17] Hackenschmidt J, Barth C and Decker K. Stimulation of acetyl-CoA carboxylase by (-)-hydroxycitrate[J]. FEBS Letters, 1972, 27(1): 131-133.

[18] Sugden M C, Steare S E, Watts D I, et al. Interactions between insulin and thyroid hormone in the control of lipogenesis[J]. Biochemical Journal, 1983, 210(3): 937-944.

[19] Sugden M C, Watts D I, Marshall C E, et al. Brown-adipose-tissue lipogenesis in starvation: Effects of insulin and (-)-hydroxycitrate[J]. Bioscience Reports, 1982, 2(5): 289-297.

[20] Ishihara K, Oyaizu S, Onuki K, et al. Chronic (-)-Hydroxycitrate administration spares carbohydrate utilization and promotes lipid oxidation during exercise in mice[J]. Journal of Nutrition, 2000, 130(12): 2990.

[21] Lim K, Ryu S, Ohishi Y, et al. Short-term (-)-hydroxycitrate ingestion increases fat oxidation during exercise in athletes[J]. Journal of Nutritional Science and Vitaminology, 2002, 48(2): 128-133.

[22] Peng M L, Han J, Li L L, et al. Metabolomics reveals the mechanism of (-)-hydroxycitric acid promotion of protein synthesis and inhibition of fatty acid synthesis in broiler chickens[J]. Animal, 2017, 12(4): 1-10.

[23] Saha A K, Vavvas D, Kurowski T G, et al. Malonyl-CoA regulation in skeletal muscle: its link to cell citrate and the glucose-fatty acid cycle[J]. American Journal of Physiology, 1997, 272(4 Pt 1): E641-648.

[24] Ruderman N B, Saha A K, Vavvas D, et al. Malonyl-CoA, fuel sensing, and insulin resistance[J]. American Journal of Physiology, 1999, 276(1): E1-E18.

[25] Preuss H G, Bagchi D, Bagchi M, et al. Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss[J]. Diabetes Obesity & Metabolism, 2004, 6(3): 171-180.

[26] Yun J K, Kim K Y, Min S K, et al. A mixture of the aqueous extract of Garcinia cambogia, soy peptide and L-carnitine reduces the accumulation of visceral fat mass in rats rendered obese by a high fat diet[J]. Genes and Nutrition, 2008, 2(4): 353-358.

[27] Mccarty M F. Promotion of hepatic lipid oxidation and gluconeogenesis as a strategy for appetite control[J]. Medical Hypotheses, 1994, 42(4): 215-225.

[28] Mccarty M F and Gustin J C. Pyruvate and hydroxycitrate/carnitine may synergize to promote reverse electron transport in hepatocyte mitochondria, effectively ‘uncoupling’ the oxidation of fatty acids[J]. Medical Hypotheses, 1999, 52(5): 407-416.

[29] Asghar M, Monjok E, Kouamou G, et al. Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation, insulin resistance, and body weight in developing obese Zucker rats[J]. Molecular and Cellular Biochemistry, 2007, 304(1-2): 93-99.

[30] Wielinga P Y, Wachters-Hagedoorn R E, Bouter B, et al. Hydroxycitric acid delays intestinal glucose absorption in rats[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2005, 288(6): G1144-1149.

[31] Nisha V M, Priyanka A, Anusree S S, et al. (-)-Hydroxycitric acid attenuates endoplasmic reticulum stress-mediated alterations in 3T3-L1 adipocytes by protecting mitochondria and downregulating inflammatory markers[J]. Free Radical Research, 2014, 48(11): 1386-1396.

[32] dos Reis S B, de Oliveira C C, Acedo S C, et al. Attenuation of colitis injury in rats using Garcinia cambogia extract[J]. Phytotherapy Research, 2009, 23(3): 324-329.

[33] Sripradha R, Sridhar M G and Maithilikarpagaselvi N. Hydroxycitric acid ameliorates high-fructose-induced redox imbalance and activation of stress sensitive kinases in male Wistar rats[J]. Journal of Basic and Clinical Physiology and Pharmacology, 2016, 27(4): 349-356.

[34] Liao C H, Sang S M, Liang Y C, et al. Suppression of inducible nitric oxide synthase and cyclooxygenase-2 in downregulating nuclear factor-kappa B pathway by Garcinol[J]. Molecular Carcinogenesis, 2004, 41(3): 140-149.

[35] Masullo M, Menegazzi M, Micco S D, et al. Direct interaction of garcinol and related polyisoprenylated benzophenones of Garcinia cambogia fruits with the transcription factor STAT-1 as a likely mechanism of their inhibitory effect on cytokine signaling pathways[J]. Journal of Natural Products, 2014, 77(3): 543-549.

[36] Balaban R S, Nemoto S and Finkel T. Mitochondria, oxidants, and aging[J]. Cell, 2005, 120(4): 483-495.

[37] Sena L A and Chandel N S. Physiological roles of mitochondrial reactive oxygen species[J]. Molecular Cell, 2012, 48(2): 158-167.

[38] Watson J A, Fang M and Lowenstein J M. Tricarballylate and hydroxycitrate: substrate and inhibitor of ATP: citrate oxaloacetate lyase[J]. Archives of Biochemistry and Biophysics, 1969, 135(1): 209-217.

[39] Cheema-Dhadli S, Halperin M L and Leznoff C C. Inhibition of enzymes which interact with citrate by (-)-hydroxycitrate and 1,2,3,-tricarboxybenzene[J]. European Journal of Biochemistry, 1973, 38(1): 98-102.

[40] Szutowicz A, Stepien M, Lysiak W, et al. Effect of (-)-hydroxycitrate on the activities of ATP citrate lyase and the enzymes of acetyl-CoA metabolism in rat brain[J]. Acta Biochimica Polonica, 1976, 23(2-3): 227-234.

[41] Soni M G, Burdock G A, Preuss H G, et al. Safety assessment of (-)-hydroxycitric acid and Super CitriMax, a novel calcium/potassium salt[J]. Food and Chemical Toxicology, 2004, 42(9): 1513-1529.

[42] Han J, Li L L, Wang D, et al. (-)-Hydroxycitric acid reduced fat deposition via regulating lipid metabolism-related gene expression in broiler chickens[J]. Lipids in Health and Disease, 2016, 15: 37.

[1] Balaji M, Ganjayi M S, Hanuma Kumar G E N, et al. A review on possible therapeutic targets to contain obesity: The role of phytochemicals[J]. Obesity Research & Clinical Practice, 2016, 10(4): 363-380.

[2] Jena B S, Jayaprakasha G K, Singh R P, et al. Chemistry and biochemistry of (-)-hydroxycitric acid from Garcinia[J]. Journal of Agricultural and Food Chemistry, 2002, 50(1): 10-22.

[3] Chuah L O, Ho W Y, Beh B K, et al. Updates on antiobesity effect of Garcinia origin (-)-HCA[J]. Evidence-Based Complementary and Alternative Medicine, 2013, 2013: 751658.

[4] Ishihara K, Oyaizu S, Onuki K, et al. Chronic (-)-hydroxycitrate administration spares carbohydrate utilization and promotes lipid oxidation during exercise in mice[J]. Journal of Nutrition, 2000, 130(12): 2990-2995.

[5] Cheng I S, Huang S W, Lu H C, et al. Oral hydroxycitrate supplementation enhances glycogen synthesis in exercised human skeletal muscle[J]. British Journal of Nutrition, 2012, 107(7): 1048-1055.

[6] Stallings W C, Blount J F, Srere P A, et al. Structural studies of hydroxycitrates and their relevance to certain enzymatic mechanisms[J]. Archives of Biochemistry and Biophysics, 1979, 193(2): 431-448.

[7] Peng M L, He Q Q, Li S N, et al. Integrated analysis of proteomics-delineated and metabolomics-delineated hepatic metabolic responses to (-)-hydroxycitric acid in chick embryos[J]. Journal of Cellular Biochemistry, 2018, 120: 1258-1270.

[8] Han N N, Li L L, Peng M L, et al. (-)-Hydroxycitric acid nourishes protein synthesis via altering metabolic directions of amino acids in male rats[J]. Phytotherapy Research, 2016, 30(8): 1316-1329.

[9] 韩宁宁, 刘冠星, 李龙龙, 等. 藤黄果提取物对高脂日粮诱导的大鼠部分组织中氨基酸谱的影响[J]. 畜牧与兽医, 2016, 48(4): 1-9.

Han N N, Liu G X, Li L L, et al. Effect of Garcinia cambogia extracts on the amino acid profile in rats fed high-fat diet[J]. Animal Husbandry & Veterinary Medicine, 2016, 48(4): 1-9 (in Chinese with English abstract).

[10] Vasques C A R, Schneider R, Klein-Júnior L C, et al. Hypolipemic effect of Garcinia cambogia in obese women[J]. Phytotherapy Research, 2014, 28(6): 887-891.

[11] Kovacs E M, Westerterp-Plantenga M S, de Vries M, et al. Effects of 2-week ingestion of (-)-hydroxycitrate and (-)-hydroxycitrate combined with medium-chain triglycerides on satiety and food intake[J]. Physiology & Behavior, 2001, 74(4-5): 543-549.

[12] Soni M G, Carabin I G and Burdock G A. Safety assessment of esters of p-hydroxybenzoic acid (parabens)[J]. Food and Chemical Toxicology, 2005, 43(7): 985-1015.

[13] Peng M L, Li L L, Yu L, et al. Effects of (-)-hydroxycitric acid on lipid droplet accumulation in chicken embryos[J]. Animal Science Journal, 2018, 89(1): 237-249.

[14] Mehlem A, Hagberg C E, Muhl L, et al. Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease[J]. Nature Protocols, 2013, 8(6): 1149-1154.

[15] Roy S, Shah H, Rink C, et al. Transcriptome of primary adipocytes from obese women in response to a novel hydroxycitric acid-based dietary supplement[J]. DNA and Cell Biology, 2007, 26(9): 627-639.

[16] Feng X J, Zhang L, Xu S W, et al. ATP-citrate lyase (ACLY) in lipid metabolism and atherosclerosis: An updated review[J]. Progress in Lipid Research, 2020, 77: 101006.

[17] Jang S R, Gornicki P, Marjanovic J, et al. Activity and structure of human acetyl-CoA carboxylase targeted by a specific inhibitor[J]. FEBS Letters, 2018, 592(12): 2048-2058.

[18] Brownsey R W, Boone A N, Elliott J E, et al. Regulation of acetyl-CoA carboxylase[J]. Biochemical Society Transactions, 2006, 34(Pt 2): 223-227.

[19] Kim Y J, Kim K Y, Kim M S, et al. A mixture of the aqueous extract of Garcinia cambogia, soy peptide and L: -carnitine reduces the accumulation of visceral fat mass in rats rendered obese by a high fat diet[J]. Genes and Nutrition, 2008, 2(4): 353-358.

[20] Kriketos A D, Thompson H R, Greene H, et al. (-)-Hydroxycitric acid does not affect energy expenditure and substrate oxidation in adult males in a post-absorptive state[J]. International Journal of Obesity and Related Metabolic Disorders, 1999, 23(8): 867-873.

[21] Agius L. Role of glycogen phosphorylase in liver glycogen metabolism[J]. Molecular Aspects of Medicine, 2015, 46: 34-45.

[22] Vestergaard H, Lund S, Larsen F S, et al. Glycogen synthase and phosphofructokinase protein and mRNA levels in skeletal muscle from insulin-resistant patients with non-insulin-dependent diabetes mellitus[J]. Journal of Clinical Investigation, 1993, 91(6): 2342-2350.

[23] Deng H B, Yu F, Chen J Q, et al. Phosphorylation of Bad at Thr-201 by JNK1 promotes glycolysis through activation of phosphofructokinase-1[J]. Journal of Biological Chemistry, 2008, 283(30): 20754-20760.

[24] Usenik A and Legi?a M. Evolution of allosteric citrate binding sites on 6-phosphofructo-1-kinase[J]. PloS One, 2010, 5(11): e15447.

[25] Peng M L, Han J, Li L L, et al. Suppression of fat deposition in broiler chickens by (-)-hydroxycitric acid supplementation: A proteomics perspective[J]. Scientific Reports, 2016, 6: 32580.

[26] Sutendra G, Kinnaird A, Dromparis P, et al. A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation[J]. Cell, 2014, 158(1): 84-97.

[27] Jones J G. Hepatic glucose and lipid metabolism. Diabetologia, 2016, 59(6): 1098-1103.

[28] Rutter J, Winge D R and Schiffman J D. Succinate dehydrogenase - Assembly, regulation and role in human disease[J]. Mitochondrion, 2010, 10(4): 393-401.

[29] Hüttemann M, Lee I, Gao X F, et al. Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology[J]. FASEB Journal, 2012, 26(9): 3916-3930.

[30] Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase[J]. Nature Medicine, 2002, 8(11): 1288-1295.

[31] Li X, Choi Y, Yanakawa Y, et al. Piperonal prevents high-fat diet-induced hepatic steatosis and insulin resistance in mice via activation of adiponectin/AMPK pathway[J]. International Journal of Obesity, 2014, 38(1): 140-147.

[32] J?rgensen S B, Richter E A and Wojtaszewski J F P. Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise[J]. Journal of Physiology, 2006, 574(Pt 1): 17-31.

[33] Pirkmajer S, Kulkarni S S, Tom R Z, et al. Methotrexate promotes glucose uptake and lipid oxidation in skeletal muscle via AMPK activation[J]. Diabetes, 2015, 64(2): 360-369.

[34] Shieh J M, Chen Y C, Lin Y C, et al. Demethoxycurcumin inhibits energy metabolic and oncogenic signaling pathways through AMPK activation in triple-negative breast cancer cells[J]. Journal of Agricultural and Food Chemistry, 2013, 61(26): 6366-6375.

[35] Wu Z, Puigserver P, Andersson U, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1[J]. Cell, 1999, 98(1): 115-124.

[36] Scarpulla R C. Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochimica et Biophysica Acta, 2002, 1576(1-2): 1-14.

[37] Viscomi C, Bottani E, Civiletto G, et al. In vivo correction of COX deficiency by activation of the AMPK/PGC-1α axis[J]. Cell Metabolism, 2011, 14(1): 80-90.

[38] Yu L and Yang S J. AMP-activated protein kinase mediates activity-dependent regulation of peroxisome proliferator-activated receptor gamma coactivator-1alpha and nuclear respiratory factor 1 expression in rat visual cortical neurons[J]. Neuroscience, 2010, 169(1): 23-38.

[39] Herzig R P, Scacco S and Scarpulla R C. Sequential serum-dependent activation of CREB and NRF-1 leads to enhanced mitochondrial respiration through the induction of cytochrome c. Journal of Biological Chemistry, 2000, 275(17): 13134-13141.

[1] Huang M Q, Zhou C J, Zhang Y P, et al. Salvianolic acid B ameliorates hyperglycemia and dyslipidemia in db/db mice through the AMPK pathway[J]. Cellular Physiology and Biochemistry, 2016, 40(5): 933-943.

[2] Roy S, Rink C, Khanna S, et al. Body weight and abdominal fat gene expression profile in response to a novel hydroxycitric acid-based dietary supplement[J]. Gene Expression, 2004, 11(5-6): 251-262.

[3] Kelly P J, Clarke P M, Hayes A J, et al. Predicting mortality in people with type 2 diabetes mellitus after major complications: a study using swedish national diabetes register data[J]. Diabetic Medicine, 2014, 31(8): 954-962.

[4] Harasiuk D, Baranowski M, Zabielski P, et al. Liver X receptor agonist TO901317 prevents diacylglycerols accumulation in the heart of streptozotocin-diabetic rats. Cellular Physiology and Biochemistry, 2016, 39: 350-359.

[5] Semwal R B, Semwal D K, Vermaak I, et al. A comprehensive scientific overview of Garcinia cambogia[J]. Fitoterapia, 2015, 102: 134-148.

[6] Hayamizu K, Hirakawa H, Oikawa D, et al. Effect of Garcinia cambogia extract on serum leptin and insulin in mice[J]. Fitoterapia, 2003, 74(3): 267-273.

[7] Vasques C A R, Rossetto S, Halmenschlager G, et al. Evaluation of the pharmacotherapeutic efficacy of Garcinia cambogia plus Amorphophallus konjac for the treatment of obesity[J]. Phytotherapy Research, 2008, 22(9): 1135-1140.

[8] Wielinga P Y, Wachters-Hagedoorn R E, Bouter B, et al. Hydroxycitric acid delays intestinal glucose absorption in rats[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2005, 288(6): G1144-G1149.

[9] Li Z, Li J, Liu X L, et al. Effects of different starch sources on glucose and fat metabolism in broiler chickens[J]. British Poultry Science, 2019, 60(4): 449-456.

[10] Nisha V M, Priyanka A, Anusree S S, et al. (-)-Hydroxycitric acid attenuates endoplasmic reticulum stress-mediated alterations in 3T3-L1 adipocytes by protecting mitochondria and downregulating inflammatory markers[J]. Free Radical Research, 2014, 48(11): 1386-1396.

[11] Cerk I K, Wechselberger L and Oberer M. Adipose triglyceride lipase regulation: An overview[J]. Current Protein & Peptide Science, 2018, 19(2): 221-233.

[12] Wang M, Ma L J, Yang Y, et al. n-3 Polyunsaturated fatty acids for the management of alcoholic liver disease: A critical review[J]. Critical Reviews in Food Science and Nutrition, 2019, 59(sup1): S116-S129.

[13] Galbraith L, Leung H Y and Ahmad I. Lipid pathway deregulation in advanced prostate cancer[J]. Pharmacological Research, 2018, 131: 177-184.

[14] Engelking L J, Cantoria M J, Xu Y C, et al. Developmental and extrahepatic physiological functions of SREBP pathway genes in mice[J]. Seminars in Cell & Developmental Biology, 2018, 81: 98-109

[15] Peng M L, Li L L, Yu L, et al. Effects of (-)-hydroxycitric acid on lipid droplet accumulation in chicken embryos[J]. Animal Science Journal, 2018, 89(1): 237-249.

[16] Rocchi S and Auwerx J. Peroxisome proliferator-activated receptor gamma, the ultimate liaison between fat and transcription[J]. British Journal of Nutrition, 2000, 84 Suppl 2: S223-S227.

[17] Fujioka S, Matsuzawa Y, Tokunaga K, et al. Improvement of glucose and lipid metabolism associated with selective reduction of intra-abdominal visceral fat in premenopausal women with visceral fat obesity[J]. International Journal of Obesity, 1991, 15(12): 853-859.

[18] Khwairakpam A D, Shyamananda M S, Sailo B L, et al. ATP citrate lyase (ACLY): A promising target for cancer prevention and treatment[J]. Current Drug Targets, 2015, 16(2): 156-163.

[19] Okamoto Y, Ogawa W, Nishizawa A, et al. Restoration of glucokinase expression in the liver normalizes postprandial glucose disposal in mice with hepatic deficiency of PDK1[J]. Diabetes, 2007, 56(4): 1000-1009.

[20] Usenik A and Legi?a M. Evolution of allosteric citrate binding sites on 6-phosphofructo-1-kinase[J]. PLoS One, 2010, 5(11): e15447.

[21] Ciszak E M, Korotchkina L G, Dominiak P M, et al. Structural basis for flip-flop action of thiamin pyrophosphate-dependent enzymes revealed by human pyruvate dehydrogenase[J]. Journal of Biological Chemistry, 2003, 278(23): 21240-21246.

[22] Weinman E O, Strisower E H and Chaikoff I L. Conversion of fatty acids to carbohydrate; application of isotopes to this problem and role of the Krebs cycle as a synthetic pathway[J]. Physiological Reviews, 1957, 37(2): 252-272.

[23] Hausladen A and Fridovich I. Measuring nitric oxide and superoxide: rate constants for aconitase reactivity[J]. Methods in Enzymology, 1996, 269: 37-41.

[24] Rutter J, Winge D R and Schiffman J D. Succinate dehydrogenase - Assembly, regulation and role in human disease[J]. Mitochondrion, 2010, 10(4): 393-401.

[25] Hochstein L I and Dalton B P. Studies of a halophilic NADH dehydrogenase. I. Purification and properties of the enzyme[J]. Biochimica et Biophysica Acta, 1973, 302(2): 216-228.

[26] Peng M L, Han J, Li L L, et al. Suppression of fat deposition in broiler chickens by (-)-hydroxycitric acid supplementation: A proteomics perspective[J]. Scientific Reports, 2016, 6: 32580.

[27] Suhane S, Berel D and Ramanujan V K. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma[J]. Biochemical and Biophysical Research Communications, 2011, 412(2): 590-595.

[28] Emahazion T, Beskow A, Gyllensten U, et al. Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain[J]. Cytogenetics and Cell Genetics, 1998, 82(1-2): 115-119.

[29] Stekhoven F S. Energy transfer factor A.D (ATP Synthetase) as a complex pi-ATP exchange enzyme and its stimulation by phospholipids[J]. Biochemical and Biophysical Research Communications, 1972, 47(1): 7-14.

[30] Fillingame R H. The proton-translocating pumps of oxidative phosphorylation[J]. Annual Review of Biochemistry, 1980, 49: 1079-1113.

[1] Hardie D G. AMPK-sensing energy while talking to other signaling pathways[J]. Cell Metabolism, 2014, 20(6): 939-952.

[2] Jeon S M. Regulation and function of AMPK in physiology and diseases[J]. Experimental and Molecular Medicine, 2016, 48(7): e245

[3] Nguyen T M D, Grasseau I and Blesbois E. New insights in the AMPK regulation in chicken spermatozoa: Role of direct AMPK activator and relationship between AMPK and PKA pathways[J]. Theriogenology, 2019, 140: 1-7.

[4] Garcia D and Shaw R J. AMPK: Mechanisms of cellular energy sensing and restoration of metabolic balance[J]. Molecular Cell, 2017, 66(6): 789-800.

[5] Liu G X, Han N N, Han J, et al. Garcinia cambogia extracts prevented fat accumulation via adiponectin AMPK signaling pathway in developing obesity rats[J]. Food Science and Technology Research, 2015, 21(6): 835-845.

[6] Proszkowiec-Weglarz M, Richards M P, Ramachandran R, et al. Characterization of the AMP-activated protein kinase pathway in chickens. Comparative Biochemistry and Physiology B-Biochemistry & Molecular Biology, 2006, 143(1): 92-106.

[7] Hardie D G, Ross F A and Hawley S A. AMPK: a nutrient and energy sensor that maintains energy homeostasis[J]. Nature Reviews Molecular Cell Biology, 2012, 13(4): 251-262.

[8] Oakhill J S, Scott J W and Kemp B E. AMPK functions as an adenylate charge-regulated protein kinase[J]. Trends in Endocrinology and Metabolism, 2012, 23(3): 125-132.

[9] Peng M L, Li L L, Yu L, et al. Effects of (-)-hydroxycitric acid on lipid droplet accumulation in chicken embryos[J]. Animal Science Journal, 2018, 89(1): 237-249.

[10] Han N N, Li L L, Peng M L, et al. (-)-Hydroxycitric acid nourishes protein synthesis via altering metabolic directions of amino acids in male rats[J]. Phytotherapy Research, 2016, 30(8): 1316-1329.

[11] Semwal R B, Semwal D K, Vermaak I, et al. A comprehensive scientific overview of Garcinia cambogia[J]. Fitoterapia, 2015, 102: 134-148.

[12] Lepropre S, Kautbally S, Octave M, et al. AMPK-ACC signaling modulates platelet phospholipids and potentiates thrombus formation[J]. Blood, 2018, 132(11): 1180-1192.

[13] Mottillo E P, Desjardins E M, Fritzen A M, et al. FGF21 does not require adipocyte AMP-activated protein kinase (AMPK) or the phosphorylation of acetyl-CoA carboxylase (ACC) to mediate improvements in whole-body glucose homeostasis[J]. Molecular Metabolism, 2017, 6(6): 471-481.

[14] Galic S, Loh K, Murray-Segal L, Steinberg G R, et al. AMPK signaling to acetyl-CoA carboxylase is required for fasting- and cold-induced appetite but not thermogenesis[J]. Elife, 2018, 7: e32656.

[15] Cheng I S, Huang S W, Lu H C, et al. Oral hydroxycitrate supplementation enhances glycogen synthesis in exercised human skeletal muscle[J]. British Journal of Nutrition, 2012, 107(7): 1048-1055.

[16] Payab M, Hasani-Ranjbar S, Shahbal N, et al. Effect of the herbal medicines in obesity and metabolic syndrome: A systematic review and meta-analysis of clinical trials[J]. Phytotherapy Research, 2020, 34(3): 526-545.

[17] Amin K A, Kamel H H, Abd Eltawab M A, et al. The relation of high fat diet, metabolic disturbances and brain oxidative dysfunction: modulation by hydroxy citric acid[J]. Lipids in Health and Disease, 2011, 10: 74.

[18] Martínez-Redondo V, Pettersson A T, Ruas J L, et al. The hitchhiker's guide to PGC-1α isoform structure and biological functions[J]. Diabetologia, 2015, 58(9): 1969-1977.

[19] Buler M, Aatsinki S M, Izzi V, et al. SIRT5 is under the control of PGC-1α and AMPK and is involved in regulation of mitochondrial energy metabolism[J]. FASEB Journal, 2014, 28(7): 3225-3237.

[20] Chaube B, Malvi P, Singh S V, et al. AMPK maintains energy homeostasis and survival in cancer cells via regulating p38/PGC-1α-mediated mitochondrial biogenesis[J]. Cell Death Discovery, 2015, 1: 15063.

[21] Yu L and Yang S J. AMP-activated protein kinase mediates activity-dependent regulation of peroxisome proliferator-activated receptor gamma coactivator-1alpha and nuclear respiratory factor 1 expression in rat visual cortical neurons[J]. Neuroscience, 2010, 169(1): 23-38

[22] Abid H, Cartier D, Hamieh A, et al. AMPK activation of PGC-1α/NRF-1-dependent SELENOT gene transcription promotes PACAP-induced neuroendocrine cell differentiation through tolerance to oxidative stress[J]. Molecular Neurobiology, 2019, 56(6): 4086-4101.

[23] Hong Y A, Bae S Y, Ahn S Y, et al. Resveratrol ameliorates contrast induced nephropathy through the activation of SIRT1-PGC-1α-Foxo1 signaling in mice[J]. Kidney & Blood Pressure Research, 2017, 42(4): 641-653.

[24] H Khan S A, Sathyanarayan A, Mashek M T, et al. ATGL-catalyzed lipolysis regulates SIRT1 to control PGC-1α/PPAR-α signaling[J]. Diabetes, 2015, 64(2): 418-426.

[1] Liu F M, Wang Q, Qian Y Z, et al. Research progress of Adenosine 5'-monophosphate-activated protein kinase in the regulation of glycolipid metabolism[J]. Chinese Journal of Biotechnology, 2019, 35: 1021-1028.

[2] Bahrami A, Barreto G E, Lombardi G, et al. Emerging roles for high-density lipoproteins in neurodegenerative disorders[J]. Biofactors, 2019, 45(5): 725-739.

[3] Ouimet M, Barrett T J and Fisher E A. HDL and reverse cholesterol transport[J]. Circulation Research, 2019, 124(10): 1505-1518.

[4] Ben-Aicha S, Badimon L and Vilahur G. Advances in HDL: Much more than lipid transporters[J]. International Journal of Molecular Sciences, 2020, 21(3): E732.

[5] Bardagjy A S and Steinberg F M. Relationship between HDL functional characteristics and cardiovascular health and potential impact of dietary patterns: a narrative review[J]. Nutrients, 2019, 11: 1231.

[6] Qu J, Ko C W, Tso P, et al. Apolipoprotein A-IV: A multifunctional protein involved in protection against atherosclerosis and diabetes[J]. Cells, 2019, 8: 319.

[7] Vlad C E, Foia L, Popescu R, et al. Apolipoproteins A and B and PCSK9: Nontraditional cardiovascular risk factors in chronic kidney disease and in end-stage renal disease[J]. Journal of Diabetes Research, 2019, 2019: 6906278.

[8] Cocuzzi E and Breckenridge W C. The biochemistry of epsilon-amino groups of lysine residues from apolipoprotein B of human low density lipoprotein[J]. Atherosclerosis, 1986, 61(1): 25-34

[9] Klein-Szanto A J P and Bassi D E. Keep recycling going: New approaches to reduce LDL-C[J]. Biochemical Pharmacology, 2019, 164: 336-341.

[10] Davis I, Yang Y, Wherritt D, et al. Reassignment of the human aldehyde dehydrogenase ALDH8A1 (ALDH12) to the kynurenine pathway in tryptophan catabolism[J]. Journal of Biological Chemistry, 2018, 293(25): 9594-9603.

[11] Viera-Vera J and García-Arrarás J E. Retinoic acid signaling is associated with cell proliferation, muscle cell dedifferentiation, and overall rudiment size during intestinal regeneration in the sea cucumber, holothuria glaberrima[J]. Biomolecules, 2019, 9(12): 873.

[12] Demirbilek H, Galcheva S, Vuralli D, et al. Ion transporters, channelopathies, and glucose disorders[J]. International Journal of Molecular Sciences, 2019, 20: 2590.

[13] Dietrich S, Jacobs S, Zheng J S, et al. Gene-lifestyle interaction on risk of type 2 diabetes: A systematic review[J]. Obesity Reviews, 2019, 20(11):1557-1571.

[14] Semba H, Takeda N, Isagawa T, et al. HIF-1α-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity[J]. Nature Communications, 2016, 7: 11635.

[15] Kim H, Cho S C, Jeong H J, et al. Indoprofen prevents muscle wasting in aged mice through activation of PDK1/AKT pathway[J]. Journal of Cachexia, Sarcopenia and Muscle, 2020.

[16] Xiao D L, Zhou Q, Gao Y B, et al. PDK1 is important lipid kinase for RANKL-induced osteoclast formation and function via the regulation of the Akt-GSK3β-NFATc1 signaling cascade[J]. Journal of Cellular Biochemistry, 2020.

[17] Lassuthova P, Rebelo A P, Ravenscroft G, et al. Mutations in ATP1A1 cause dominant charcot-marie-tooth type 2[J]. American Journal of Human Genetics, 2018, 102(3): 505-514.

[18] Yu Y, Chen C, Huo G, et al. ATP1A1 integrates AKT and ERK signaling via potential interaction with src to promote growth and survival in glioma stem cells[J]. Frontiers in Oncology, 2019, 9: 320-320.

[19] Wang L H, Han X J, Qu G J, et al. A pH probe inhibits senescence in mesenchymal stem cells[J]. Stem Cell Research & Therapy, 2018, 9(1): 343.

[20] Higashida H, Yokoyama S, Tsuji C, et al. Neurotransmitter release: vacuolar ATPase V0 sector c-subunits in possible gene or cell therapies for parkinson's, alzheimer's, and psychiatric diseases[J]. Journal of Physiological Sciences, 2017, 67(1): 11-17.

[21] Yang L H. Neuronal cAMP/PKA Signaling and Energy Homeostasis[J]. Advances in Experimental Medicine and Biology, 2018, 1090: 31-48.

[22] Goudarzvand M, Afraei S, Yaslianifard S, et al. Hydroxycitric acid ameliorates inflammation and oxidative stress in mouse models of multiple sclerosis[J]. Neural Regeneration Research, 2016, 11(10): 1610-1616.

[23] Nisha V M, Priyanka A, Anusree S S, et al. (-)-Hydroxycitric acid attenuates endoplasmic reticulum stress-mediated alterations in 3T3-L1 adipocytes by protecting mitochondria and downregulating inflammatory markers[J]. Free Radical Research, 2014, 48(11): 1386-1396.

[24] Petriz B A, Almeida J A, Gomes C P C, et al. NanoUPLC/MS(E) proteomic analysis reveals modulation on left ventricle proteome from hypertensive rats after exercise training[J]. Journal of Proteomics, 2015, 113: 351-365.

[25] Dubiel W, Dubiel D, Wolf D A, et al. Cullin 3-based ubiquitin ligases as master regulators of mammalian cell differentiation[J]. Trends in Biochemical Sciences, 2018, 43(2): 95-107.

[26] Hua Z H and Vierstra R D. The cullin-RING ubiquitin-protein ligases[J]. Annual Review of Plant Biology, 2011, 62: 299-334.

[27] Kiss L, Zeng J W, Dickson C F, et al. A tri-ionic anchor mechanism drives Ube2N-specific recruitment and K63-chain ubiquitination in TRIM ligases[J]. Nature Communications, 2019, 10(1): 4502.

[28] Czub B, Shah A Z, Alfano G, et al. TOPORS, a dual E3 ubiquitin and sumo1 ligase, interacts with 26 S protease regulatory subunit 4, encoded by the PSMC1 gene[J]. PloS One, 2016, 11(2): e0148678.

[29] Ahn S H, Deshmukh H, Johnson N, et al. Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses[J]. PLoS Pathogens, 2010, 6(9): e1001088.

[30] Asakawa H, Kojidani T, Yang H J, et al. Asymmetrical localization of Nup107-160 subcomplex components within the nuclear pore complex in fission yeast[J]. PLoS Genetics, 2019, 15(6): e1008061.

[1] Gibellini L, De Biasi S, Nasi M, et al. Mitochondrial proteases as emerging pharmacological targets[J]. Current Pharmaceutical Design, 2016, 22(18): 2679-2688.

[2] Hernández-Aguilera A, Rull A, Rodríguez-Gallego E, et al. Mitochondrial dysfunction: a basic mechanism in inflammation-related non-communicable diseases and therapeutic opportunities[J]. Mediators of Inflammation, 2013, 2013: 135698.

[3] de Mello A H, Costa A B, Engel J D G, et al. Mitochondrial dysfunction in obesity[J]. Life Sciences, 2018, 192: 26-32.

[4] Arruda A P, Pers B M, Parlakgül G, et al. Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity[J]. Nature Medicine, 2014, 20(12): 1427-1435.

[5] Cheung P C, Salt I P, Davies S P, et al. Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding[J]. Biochemical Journal, 2000, 346(Pt 3): 659-669.

[6] Carling D. AMPK signalling in health and disease[J]. Current Opinion in Cell Biology, 2017, 45: 31-37.

[7] Herzig S and Shaw R J. AMPK: guardian of metabolism and mitochondrial homeostasis[J]. Nature Reviews Molecular Cell Biology, 2018, 19(2): 121-135.

[8] Lin S C and Hardie D G. AMPK: sensing glucose as well as cellular energy status[J]. Cell Metabolism, 2018, 27(2): 299-313.

[9] Misu H, Takayama H, Saito Y, et al. Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle[J]. Nature Medicine, 2017, 23(4): 508-516.

[10] Jalmi S K and Sinha A K. ROS mediated MAPK signaling in abiotic and biotic stress-striking similarities and differences[J]. Frontiers in Plant Science, 2015, 6: 769.

[11] Huang K, Liang Q, Zhou Y, et al. A novel allosteric inhibitor of phosphoglycerate mutase 1 suppresses growth and metastasis of non-small-cell lung cancer[J]. Cell Metabolism, 2019, 30(6): 1107-1119.

[12] Hu G, Hong D, Zhang T, et al. Cynatratoside-c from cynanchum atratum displays anti-inflammatory effect via suppressing TLR4 mediated NF-κB and MAPK signaling pathways in LPS-induced mastitis in mice[J]. Chemico-Biological Interactions, 2018, 279: 187-195.

[13] Amin K A, Kamel H H and Abd Eltawab M A. The relation of high fat diet, metabolic disturbances and brain oxidative dysfunction: modulation by hydroxy citric acid[J]. Lipids in Health and Disease, 2011, 10: 74.

[14] Semwal R B, Semwal D K, Vermaak I, et al. A comprehensive scientific overview of Garcinia cambogia[J]. Fitoterapia, 2015, 102: 134-148.

[15] Goudarzvand M, Afraei S, Yaslianifard S, et al. Hydroxycitric acid ameliorates inflammation and oxidative stress in mouse models of multiple sclerosis[J]. Neural Regeneration Research, 2016, 11(10): 1610-1616.

[16] Nisha V M, Priyanka A, Anusree S S, et al. (-)-Hydroxycitric acid attenuates endoplasmic reticulum stress-mediated alterations in 3T3-L1 adipocytes by protecting mitochondria and downregulating inflammatory markers[J]. Free Radical Research, 2014, 48(11): 1386-1396.

[17] Verdile G, Keane K N, Cruzat V F, et al. Inflammation and oxidative stress: the molecular connectivity between insulin resistance, obesity, and alzheimer's disease[J]. Mediators of Inflammation, 2015, 2015: 105828.

[18] Qiao R, Sheng C, Lu Y, et al. Microplastics induce intestinal inflammation, oxidative stress, and disorders of metabolome and microbiome in zebrafish[J]. Science of the Total Environment, 2019, 662: 246-253.

[19] Steven S, Dib M, Hausding M, et al. CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice[J]. Cardiovascular Research, 2018, 114(2): 312-323.

[20] Fu M, Zhang W H, Wu L Y, et al. Hydrogen sulfide (H2S) metabolism in mitochondria and its regulatory role in energy production[J]. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(8): 2943-2948.

[21] Wu M Y, Yiang G T, Lai T T, et al. The oxidative stress and mitochondrial dysfunction during the pathogenesis of diabetic retinopathy[J]. Oxidative Medicine and Cellular Longevity, 2018, 2018: 3420187.

[22] Niemann B, Rohrbach S, Miller M R, et al. Oxidative stress and cardiovascular risk: obesity, diabetes, smoking, and pollution: part 3 of a 3-part series[J]. Journal of the American College of Cardiology, 2017, 70(2): 230-251.

[23] Kim M H, Seong J B, Huh J W, et al. Peroxiredoxin 5 ameliorates obesity-induced non-alcoholic fatty liver disease through the regulation of oxidative stress and AMP-activated protein kinase signaling[J]. Redox Biology, 2020, 28: 101315.

[24] Kukidome D, Nishikawa T, Sonoda K, et al. Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells[J]. Diabetes, 2006, 55(1): 120-127.

[25] Ojuka E O. Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle[J]. Proceedings of the Nutrition Society, 2004, 63(2): 275-278.

[26] Lu Z, Xu X, Hu X, et al. PGC-1 alpha regulates expression of myocardial mitochondrial antioxidants and myocardial oxidative stress after chronic systolic overload[J]. Antioxidants & Redox Signaling, 2010, 13(7): 1011-1022.

[27] Scarpulla R C. Transcriptional paradigms in mammalian mitochondrial biogenesis and function[J] Physiological Reviews, 2008, 88(2): 611-638.

[28] Scarpulla R C. Nuclear control of respiratory gene expression in mammalian cells[J]. Journal of Cellular Biochemistry, 2006, 97(4): 673-683.

[29] Pe?a-Blanco A and García-Sáez A J. Bax, bak and beyond-mitochondrial performance in apoptosis[J]. FEBS Journal, 2018, 285(3): 416-431.

[30] Wang J, Yuan L, Xiao H F, et al. Momordin ic induces HepG2 cell apoptosis through MAPK and PI3K/Akt-mediated mitochondrial pathways[J]. Apoptosis, 2013, 18(16): 751-765.

[31] Senthil V, Ramadevi S, Venkatakrishnan V, et al. Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase activation[J]. Chemico-Biological Interactions, 2007, 167(1): 19-30.