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 non-adipose 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.Supplementing male Wistar rats with 0.5% ALA for eight weeks significantly reduced body weight, both on low- and high-fat diets (-24% LFD+ALA vs. LFD, p<0.01, and -29% HFD+ALA vs. HFD, p<0.001). Oil red O lipid staining revealed a three-fold higher lipid content in skeletal muscle after HFD compared to LFD and ALA-supplemented groups (p<0.05). ALA improved whole body glucose tolerance ( approximately 20% lower total 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 high-fat diet-induced muscular lipid accumulation and the improved whole body glucose tolerance are likely secondary effects due to the anorexic nature of ALA.
- AMP-activated protein kinase
- intramyocellular lipid accumulation
- glucose tolerance
- MITOCHONDRIAL BIOGENESIS
- INSULIN SENSITIVITY
- THIOCTIC ACID
Timmers, S., Bosch, J., Towler, M. C., Schaart, G., Kornips, E., Mensink, R. P., Hesselink, M. K., Hardie, D. G., & Schrauwen, P. (2010). Prevention of high-fat diet-induced muscular lipid accumulation in rats by alpha lipoic acid is not mediated by AMPK activation. Journal of Lipid Research, 51(2), 352-359. https://doi.org/10.1194/jlr.M000992