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

S. Timmers, J. Bosch, M.C. Towler, G. Schaart, E. Kornips, R.P. Mensink, M.K. Hesselink, D.G. Hardie, P. Schrauwen

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14 Citations (Scopus)

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 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.
Original languageEnglish
Pages (from-to)352-359
Number of pages8
JournalJournal of Lipid Research
Volume51
Issue number2
DOIs
Publication statusPublished - Feb 2010

Keywords

  • AMP-activated protein kinase
  • intramyocellular lipid accumulation
  • glucose tolerance
  • PROTEIN-KINASE
  • SKELETAL-MUSCLE
  • DIABETES-MELLITUS
  • MITOCHONDRIAL BIOGENESIS
  • INSULIN SENSITIVITY
  • GLUCOSE-TRANSPORT
  • THIOCTIC ACID
  • FOOD-INTAKE
  • METABOLISM
  • EXPRESSION

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