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A high-fat diet decreases bone mass in growing mice with systemic chronic inflammation induced by low-dose, slow-release lipopolysaccharide pellets

Jay J. Cao, Brian R. Gregoire, Chwan-Li Shen
Journal of Nutrition 2017 v.147 no.10 pp. 1909-1916
acid phosphatase, adipose tissue, biomarkers, blood serum, bone density, bone marrow, bone resorption, energy, females, femur, high fat diet, inflammation, interleukin-1beta, interleukin-6, lipopolysaccharides, lumbar spine, mass, mice, models, obesity, osteoclasts, osteopenia, pellets, placebos, tumor necrosis factor-alpha, vertebrae
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.