Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes
| Autor: | Yu Shiou Wang, Chih Cheng Chang, Kur Ta Cheng, Hsiu Chu Chou, Ching Kuo Lee, Shu Hui Juan |
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| Rok vydání: | 2015 |
| Předmět: |
Pharmacology
chemistry.chemical_classification medicine.medical_specialty biology Pharmaceutical Science AMPK Peroxisome proliferator-activated receptor Endocrinology Complementary and alternative medicine AMP-activated protein kinase chemistry Internal medicine Drug Discovery Adipose triglyceride lipase biology.protein medicine Molecular Medicine Lipolysis Carnitine O-palmitoyltransferase Carnitine palmitoyltransferase I Mitochondrial transport |
| Zdroj: | Phytomedicine. 22:641-647 |
| ISSN: | 0944-7113 |
| Popis: | 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 β-oxidation. We also demonstrated that kinsenoside increased the phosphorylation of peroxisome proliferator-activated receptor alpha (PPARα) and CRE-binding protein (CREB), and the protein levels of silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and carnitine palmitoyltransferase I (CPT1) through an AMPK-dependent mechanism. SIRT1 deacetylated PGC-1α, facilitating AMPK-mediated PGC-1α phosphorylation and increasing the interaction of PPARα with its coactivator, PGC-1α. 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-1α 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. |
| Databáze: | OpenAIRE |
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