Prevention of high-fat diet-induced muscular lipid accumulation in rats by alpha lipoic acid is not mediated by AMPK activation.

Abstract

Skeletal muscle triglyceride accumulation is associated with insulin resistance in obesity. Recently, it has been suggested that alpha lipoic acid (ALA) improves insulin sensitivity by lowering triglyceride accumulation in nonadipose tissues via activation of skeletal muscle AMP-activated protein kinase (AMPK). We examined whether chronic ALA supplementation prevents muscular lipid accumulation that is associated with high-fat diets via activation of AMPK. In addition, we tested if ALA supplementation was able to improve insulin sensitivity in rats fed low- and high-fat diets (LFD, HFD). Supplementing male Wistar rats with 0.5% ALA for 8 weeks significantly reduced body weight, both on LFD and HFD (-24% LFD+ALA vs. LFD, P < 0.01, and -29% HFD+ALA vs. HFD, P < 0.001). Oil red O lipid staining revealed a 3-fold higher lipid content in skeletal muscle after HFD compared with LFD and ALA-supplemented groups (P < 0.05). ALA improved whole body glucose tolerance ( approximately 20% lower total area under the curve (AUC) in ALA supplemented groups vs. controls, P < 0.05). These effects were not mediated by increased muscular AMPK activation or ALA-induced improvement of muscular insulin sensitivity. To conclude, the prevention of HFD-induced muscular lipid accumulation and the improved whole body glucose tolerance are likely secondary effects due to the anorexic nature of ALA.

• Authors: Silvie Timmers, Johan de Vogel-van den Bosch, Mhairi C Towler, Gert Schaart, Esther Moonen-Kornips, Ronald P Mensink, Matthijs K Hesselink, D Grahame Hardie, Patrick Schrauwen
• Journal: Journal of lipid research (J Lipid Res) Vol. 51 Issue 2 Pg. 352-9 (Feb 2010) ISSN: 1539-7262 [Electronic] United States
• PMID: 19690335 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Insulin
• Thioctic Acid
• AMP-Activated Protein Kinases
• Glucose

Topics

• AMP-Activated Protein Kinases (metabolism)
• Absorption (drug effects)
• Adult
• Animals
• Body Composition (drug effects)
• Body Weight (drug effects)
• Dietary Fats (pharmacology)
• Dietary Supplements
• Eating (drug effects)
• Enzyme Activation (drug effects)
• Glucose (metabolism)
• Glucose Tolerance Test
• Humans
• Insulin (metabolism)
• Lipid Metabolism (drug effects)
• Male
• Muscle, Skeletal (drug effects, metabolism)
• Muscles (drug effects, metabolism)
• Obesity (chemically induced, metabolism, physiopathology, prevention & control)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)
• Thioctic Acid (administration & dosage, pharmacology)