Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/3/2017
Publication Date: N/A
Citation: N/A Interpretive Summary: Chronic inflammation exists in a variety of physiological conditions such as aging, menopause, as well as obesity, and it is linked to increased bone resorption and bone loss. Using a rodent model, we investigated whether high-fat diet induced obesity would further compromise bone health during systemic, chronic inflammation. We demonstrated that both obesity and inflammation increased bone resorption and were detrimental to bone structure. Our data indicate that an obesogenic diet and systemic inflammation have independent effects rather than synergistic negative effects on bone-related parameters. These findings suggest that reducing excessive adiposity could be helpful to improve bone health in chronic inflammation states such as aging and postmenopausal estrogen deficiency.
Technical Abstract: Chronic inflammation is linked to osteopenia or low bone mass, observed in a variety of physiological conditions such as aging and post-menopause with estrogen deficiency. Evidence suggests that obesity is also associated with low-grade chronic up-regulation of inflammatory cytokines. This study investigated the effect of obesity on bone loss with existing systemic chronic inflammation induced by low-dose, slow-release lipopolysaccharide (LPS). Forty-eight 6-wk-old female C57BL/6 mice were randomly assigned to four treatment groups (n=12/group) in a 2 x 2 factorial design: control (placebo) or LPS treatment (1.5 µg/d) and fed either a normal-fat (NF, 10% energy as fat) or a high-fat (HF, 45% energy as fat) diet ad libitum for 13 wks. No alterations were observed in final body weights, fat mass, and lean mass in response to LPS treatment. LPS treatment increased serum concentration of tartrate-resistant acid phosphatase (TRAP, a bone resorption marker), bone marrow osteoclast differentiation, and induced bone loss. Mice fed the HF diet had greater body weight at the end of the study (p < 0.01) mainly due to increased fat mass (p < 0.01) than animals fed the NF diet. Obesity increased serum TRAP concentration, bone marrow osteoclast differentiation, and expression of TNF-a, IL-1ß, and IL-6 in adipose tissue. The HF diet was detrimental to bone structure with decreased bone volume/total volume and Tb.N and increased trabecular separation and structure model index, compared to the NF diet. Mice treated with LPS and fed the high-fat diet had the lowest bone volume at either distal femur or 2nd lumbar vertebrae. These results suggest that obesity further compromises bone loss in systemic chronic inflammation.