Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes Roles of AMPK and PPARα in the lipolytic effect of kinsenoside
Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes Roles of AMPK and PPARα in the lipolytic effect of kinsenoside
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DOI：
10.1016/j.phymed.2015.04.001
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发表时间：
2015-06-01
期刊：
影响因子：
7.9
通讯作者：
Juan, Shu-Hui
中科院分区：
文献类型：
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作者：
Cheng, Kur-Ta;Wang, Yu-Shiou;Juan, Shu-Hui
背景资料：目前，全球超过三分之一的人口超重或肥胖，这是导致心血管疾病、多种癌症和糖尿病等主要死亡原因的风险因素。金线莲的主要活性成分之一，具有降血糖、降血脂和保肝作用，可用于预防和控制肥胖症。目的：本研究检测了金线莲皂苷对C3 H10 T1/2细胞转化的脂肪细胞中脂肪分解的分解代谢作用。采用油红O染色法和甘油生成法检测Kinsenoside对C3 H10 T1/2脂肪细胞的脂解作用。通过Western印迹，染色质免疫沉淀（IP），Co-IP，EMSA和siRNA verifiation.Results的潜在机制进行了评估：我们证明，金森甙增加脂肪甘油三酯脂肪酶（ATGL）介导的脂解，这是上调AMP激活的蛋白激酶（AMPK）的激活，和甘油三酯水解为甘油和脂肪酸，需要运输到线粒体进一步β-氧化。我们还证明，通过AMPK依赖性机制，Kinsenoside增加了过氧化物酶体增殖物激活受体α（PPAR α）和CREB结合蛋白（CREB）的磷酸化，以及沉默信息调节因子T1（SIRT 1）、过氧化物酶体增殖物激活受体γ共激活因子-1 α（PGC-1 α）和肉毒碱棕榈酰转移酶I（CPT 1）的蛋白水平。SIRT 1使PGC-1 α去乙酰化，促进AMPK介导的PGC-1 α磷酸化，并增加PPAR α与其辅激活因子PGC-1 α的相互作用。这种相互作用提高了CPT 1的表达，CPT 1是一种用于线粒体转运脂肪酸的穿梭剂，在kinsenoside处理的细胞中。此外，AMPK磷酸化介导的CREB激活引起的kinsenoside介导的PGC-1 alpha upregulation.Conclusion：AMPK激活不仅提高ATGL的脂肪分解的表达，但也诱导CPT 1的表达进一步线粒体易位的脂肪酸。结果表明，潜在的机制的kinsenoside对脂肪分解和增加CPT 1诱导的分解代谢作用是通过AMPK依赖性途径介导的。(C)2015 Elsevier GmbH. All rights reserved.
Background: Currently, more than one-third of the global population is overweight or obese, which is a risk factor for major causes of death including cardiovascular disease, numerous cancers, and diabetes. Kinsenoside, a major active component of Anoectochilus formosanus exhibits antihyperglycemic, antihyperliposis, and hepatoprotective effects and can be used to prevent and manage obesity.Purpose: This study examined the catabolic effects of kinsenoside on lipolysis in adipocytes transformed from C3H10T1/2 cells.Study design/methods: The lipolytic effect of kinsenoside in C3H10T1/2 adipocytes was evaluated by oil-red O staining and glycerol production. The underlying mechanisms were assessed by Western blots, chromatin immunoprecipitation (IP), Co-IP, EMSA and siRNAs verification.Results: We demonstrated that kinsenoside increased both adipose triglyceride lipase (ATGL)-mediated lipolysis, which was upregulated by AMP-activated protein kinase (AMPK) activation, and the hydrolysis of triglycerides to glycerol and fatty acids that require transportation into mitochondria for further beta-oxidation. We also demonstrated that kinsenoside increased the phosphorylation of peroxisome proliferotor-activated receptor alpha (PPAR alpha) and CRE-binding protein (CREB), and the protein levels of silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) and carnitine palmitoyltransferase I (CPT1) through an AMPK-dependent mechanism. SIRT1 deacetylated PGC-1 alpha, facilitating AMPK-mediated PGC-1 alpha phosphorylation and increasing the interaction of PPAR alpha with its coactivator, PGC-1 alpha. This interaction elevated the expression of CPT1, a shuttle for the mitochondrial transport of fatty acids, in kinsenoside-treated cells. In addition, AMPK-phosphorylation-mediated CREB activation caused kinsenoside-mediated PGC-1 alpha upregulation.Conclusion: AMPK activation not only elevated ATGL expression for lipolysis but also induced CPT1 expression for further mitochondrial translocation of fatty acids. The results suggested that the mechanism underlying the catabolic effects of kinsenoside on lipolysis and increased CPT1 induction was mediated through an AMPK-dependent pathway. (C) 2015 Elsevier GmbH. All rights reserved.