Abstract | AIMS/HYPOTHESIS:
Sirtuin 1 ( SIRT1) is a longevity-associated protein, which regulates energy metabolism and lifespan in response to nutrient deprivation. It has been proposed to be a therapeutic target for obesity and metabolic syndrome. We investigated whether α- lipoic acid (ALA) exerts a lipid-lowering effect through regulation of SIRT1 activation and production in C(2)C(12) myotubes. METHODS: RESULTS: ALA increased the NAD(+)/ NADH ratio to enhance SIRT1 activity and production in C(2)C(12) myotubes. ALA subsequently increased AMPK and ACC phosphorylation, leading to increased palmitate β-oxidation and decreased intracellular triacylglycerol accumulation in C(2)C(12) myotubes. In cells treated with nicotinamide or transfected with SIRT1 siRNA, ALA-mediated AMPK/ACC phosphorylation, intracellular triacylglycerol accumulation and palmitate β-oxidation were reduced, suggesting that SIRT1 is an upstream regulator of AMPK. ALA increased ATGL and suppressed FAS protein production in C(2)C(12) myotubes. Oral administration of ALA in diabetic mice fed on a high-fat diet and db/db mice dramatically reduced the body weight and visceral fat content. CONCLUSIONS/INTERPRETATION: ALA activates both SIRT1 and AMPK, which leads to lipid-lowering effects in vitro and in vivo. These findings suggest that ALA may have beneficial effects in the treatment of dyslipidaemia and obesity.
|
Authors | W-L Chen, C-H Kang, S-G Wang, H-M Lee |
Journal | Diabetologia
(Diabetologia)
Vol. 55
Issue 6
Pg. 1824-35
(Jun 2012)
ISSN: 1432-0428 [Electronic] Germany |
PMID | 22456698
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Palmitates
- Triglycerides
- Thioctic Acid
- AMP-Activated Protein Kinases
- Sirtuin 1
|
Topics |
- AMP-Activated Protein Kinases
(genetics, metabolism)
- Animals
- Cell Line
- Diabetes Mellitus, Experimental
(metabolism)
- Lipid Metabolism
(drug effects, genetics)
- Liver
(metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Muscles
(metabolism)
- Oxidation-Reduction
(drug effects)
- Palmitates
(metabolism)
- Sirtuin 1
(genetics, metabolism)
- Thioctic Acid
(pharmacology)
- Triglycerides
(metabolism)
|