Lipoic acid increases the expression of genes involved in bone formation in mice fed a high-fat diet

Nutr Res. 2011 Apr;31(4):309-17. doi: 10.1016/j.nutres.2011.03.013.


Antioxidant lipoic acid (LA) has been reported to have a potential prophylactic effect on bone loss induced by high-fat diet (HFD). The aim of this work was to examine the hypothesis that LA decreases bone resorption-related gene expression and increases bone formation-related gene expression in HFD-fed mice, preventing a shift in the bone metabolism balance toward resorption. Male C57BL/6 mice were fed a normal diet, HFD, or HFD plus 0.1% LA for 12 weeks. The bone metabolism-related genes differentially expressed between mice fed HFD and those fed HFD supplemented with LA were identified through complementary DNA microarray. The supplemental LA significantly increased bone mineral density and bone antioxidant capacity in mice fed HFD (P < .05). Compared with the HFD-fed mice, LA induced the decreased expression of genes associated with bone resorption, such as Mmp9 (1.9-fold) and Ctsk (2.3-fold), and increased those genes associated with bone formation, such as Col1a1 (1.3-fold) and Alp1 (1.5-fold). Furthermore, LA upregulated many genes involved in the Igf signaling pathway, such as Igf-1 (increased 1.7-fold), and downregulated genes involved in the p53 apoptotic pathway, such as p53 (decreased 2.3-fold), thus attenuating the HFD-induced inhibition of bone formation. Lipoic acid induced upregulation of Il12a (2.1-fold) and downregulation of Tgfbr1 (4.3-fold) and Il17a (11.3-fold), which may reduce bone resorption. In summary, LA supplementation during HFD could affect bone density, altering gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Dietary Fats / administration & dosage*
  • Dietary Supplements
  • Down-Regulation
  • Gene Expression / drug effects*
  • Insulin-Like Growth Factor I / metabolism
  • Interleukin-12 Subunit p35 / genetics
  • Interleukin-17 / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics*
  • Oxidative Stress
  • Protein Serine-Threonine Kinases / genetics
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Thioctic Acid / administration & dosage*
  • Up-Regulation


  • Biomarkers
  • Dietary Fats
  • Il12a protein, mouse
  • Il17a protein, mouse
  • Interleukin-12 Subunit p35
  • Interleukin-17
  • Receptors, Transforming Growth Factor beta
  • Insulin-Like Growth Factor I
  • Thioctic Acid
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • Tgfbr1 protein, mouse