A High-Fat Diet Decreases Bone Mass in Growing Mice with Systemic Chronic Inflammation Induced by Low-Dose, Slow-Release Lipopolysaccharide Pellets

J Nutr. 2017 Oct;147(10):1909-1916. doi: 10.3945/jn.117.248302. Epub 2017 Aug 16.


Background: Chronic inflammation is associated with increased bone resorption and is linked to osteopenia, or low bone mass. Obesity is also associated with low-grade chronic upregulation of inflammatory cytokines.Objective: This study investigated the effect of high-fat (HF) diet-induced obesity on bone structure changes in growing mice with existing systemic chronic inflammation induced by low-dose, slow-release lipopolysaccharide (LPS).Methods: Forty-eight 6-wk-old female C57BL/6 mice were randomly assigned to 4 treatment groups (n = 12/group) in a 2 × 2 factorial design-control (placebo) or LPS treatment (1.5 μg/d)-and consumed either a normal-fat (NF, 10% of energy as fat) or an HF (45% of energy as fat) diet ad libitum for 13 wk. Bone structure, serum biomarkers of bone turnover, and osteoclast differentiation were measured.Results: No alterations were observed in final body weights, fat mass, or lean mass in response to LPS treatment. LPS treatment increased serum concentration of tartrate-resistant acid phosphatase (TRAP, a bone resorption marker) and bone marrow osteoclast differentiation and decreased femoral and lumbar vertebral bone volume (BV):total volume (TV) by 25% and 24%, respectively, compared with the placebo. Mice fed the HF diet had greater body weight at the end of the study (P < 0.01) due to increased fat mass (P < 0.01) than did mice fed the NF diet. The HF diet increased serum TRAP concentration, bone marrow osteoclast differentiation, and expression of tumor necrosis factor α, interleukin 1β and interleukin 6 in adipose tissue. Compared with the NF diet, the HF diet decreased BV:TV by 10% and 8% at femur and lumbar vertebrae, respectively, and the HF diet was detrimental to femoral and lumbar vertebral bone structure with decreased trabecular number and increased trabecular separation and structure model index.Conclusion: Results suggest that HF diets and systemic chronic inflammation have independent negative effects on bone structure in mice.

Keywords: bone structure; high-fat diet; inflammation; lipopolysaccharide; obesity.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers / blood
  • Bone Density*
  • Bone Diseases, Metabolic / etiology*
  • Bone Diseases, Metabolic / metabolism
  • Bone Remodeling
  • Bone and Bones / cytology
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Cell Differentiation
  • Diet, High-Fat*
  • Dietary Fats / administration & dosage
  • Dietary Fats / adverse effects*
  • Female
  • Femur / drug effects
  • Femur / metabolism
  • Inflammation / blood
  • Inflammation / complications*
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Lipopolysaccharides
  • Lumbar Vertebrae / drug effects
  • Lumbar Vertebrae / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Obesity / blood
  • Obesity / complications*
  • Osteoclasts / drug effects
  • Osteoclasts / physiology
  • Random Allocation
  • Tartrate-Resistant Acid Phosphatase / blood
  • Tumor Necrosis Factor-alpha / blood


  • Biomarkers
  • Dietary Fats
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Tartrate-Resistant Acid Phosphatase