Dyslipidemic high-fat diet affects adversely bone metabolism in mice associated with impaired antioxidant capacity

Nutrition. 2011 Feb;27(2):214-20. doi: 10.1016/j.nut.2009.11.012. Epub 2010 Apr 14.


Objective: The present study examined impacts of dyslipidemic high-fat diet on the bone antioxidant system and bone metabolism in growing mice. Furthermore, the relationship was studied between them.

Methods: Male C57BL/6 mice (4 wk old) were fed with normal diet, high-fat diet (HFD), or HFD supplemented with 0.1% antioxidant lipoic acid (LA). After 13-wk feeding, the markers of plasma lipids status, bone metabolism in plasma and in urine, and femora oxidative stress were measured. To provide molecular evidence for abnormal bone metabolism affected by HFD, bone cell-specific mRNA levels were tested by real-time quantitative polymerase chain reaction. Moreover, insulin-like growth factor I and tumor necrosis factor-alpha in plasma and their mRNA levels in femur were measured.

Results: The feeding dyslipidemic HFD induced both inhibitory bone formation reactions and enhancement of bone resorption reactions, accompanied by impaired bone antioxidant system, low levels of insulin-like growth factor I in plasma and in bone, and high levels of tumor necrosis factor-alpha in plasma but not in bone. In contrast, these alternatives were prevented completely or partially in mice fed LA supplement. Further, plasma propeptide of І collagen C-propeptide as a marker of bone formation was positively correlated with both total antioxidant capacity (r=0.683, P<0.001) and reduced glutathione/oxidized glutathione ratio (r=0.565, P<0.003) of bone. Cross-linked N-telopeptides of bone type І collagen as a marker of bone resorption was negatively correlated with both total antioxidant capacity (r=-0.753, P<0.001) and glutathione/oxidized glutathione ratio (r=-0.786, P<0.001).

Conclusion: Dyslipidemia induces impaired bone antioxidant system. Oxidative stress could be an important mediator of hyperlipidemia-induced bone loss.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / metabolism*
  • Bone Resorption / physiopathology
  • Bone and Bones / metabolism*
  • Collagen Type I / blood
  • Dietary Fats / administration & dosage*
  • Dietary Fats / adverse effects*
  • Disease Models, Animal
  • Down-Regulation
  • Femur / chemistry
  • Hyperlipidemias / physiopathology*
  • Insulin-Like Growth Factor I / analysis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteoblasts / metabolism
  • Osteoclasts / metabolism
  • Oxidative Stress
  • Peptides / blood
  • Random Allocation
  • Thioctic Acid / administration & dosage
  • Thioctic Acid / metabolism*
  • Tumor Necrosis Factor-alpha / blood


  • Antioxidants
  • Collagen Type I
  • Dietary Fats
  • Peptides
  • Tumor Necrosis Factor-alpha
  • collagen type I trimeric cross-linked peptide
  • Insulin-Like Growth Factor I
  • Thioctic Acid