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Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes: Roles of AMPK and PPARα in the lipolytic effect of kinsenoside.

AbstractBACKGROUND:
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.
AuthorsKur-Ta Cheng, Yu-Shiou Wang, Hsiu-Chu Chou, Chih-Cheng Chang, Ching-Kuo Lee, Shu-Hui Juan
JournalPhytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 22 Issue 6 Pg. 641-7 (Jun 01 2015) ISSN: 1618-095X [Electronic] Germany
PMID26055129 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier GmbH. All rights reserved.
Chemical References
  • 3-glucopyranosyloxybutanolide
  • Fatty Acids
  • Monosaccharides
  • PPAR alpha
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Transcription Factors
  • Carnitine O-Palmitoyltransferase
  • AMP-Activated Protein Kinases
  • Sirt1 protein, mouse
  • Sirtuin 1
  • 4-Butyrolactone
  • Glycerol
Topics
  • 4-Butyrolactone (analogs & derivatives, pharmacology)
  • AMP-Activated Protein Kinases (metabolism)
  • Adipocytes (drug effects, metabolism)
  • Animals
  • Carnitine O-Palmitoyltransferase (metabolism)
  • Cell Line
  • Fatty Acids (metabolism)
  • Glycerol (metabolism)
  • Lipolysis
  • Mice
  • Mitochondria (metabolism)
  • Monosaccharides (pharmacology)
  • PPAR alpha (metabolism)
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Signal Transduction
  • Sirtuin 1
  • Transcription Factors (metabolism)

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