ARS | Publication request: Obesity induced by high dietary fat leads to increased bone resorption marker, TRAP, and decreased bone mass in mice

Submitted to: Meeting Abstract
Publication Type: Abstract
Publication Acceptance Date: May 1, 2008
Publication Date: August 12, 2008
Citation: Cao, J.J., Gregoire, B.R., Gao, H. 2008. Obesity induced by high dietary fat leads to increased bone resorption marker, TRAP, and decreased bone mass in mice [Abstract]. 23S1:432.

Technical Abstract: Obesity, which is growing in prevalence, is a risk factor for such chronic health disorders as diabetes and cardiovascular diseases. However, it is thought to be a protective factor for osteoporosis and bone fractures in humans. Accumulating data in humans suggest that fat mass has a negative effect on bone when the confounding factor, mechanical loading of body weight in obesity, was removed. Furthermore, obesity is associated with the chronic up-regulation of inflammatory cytokines such as TNF-a, IL-1ß, IL-6, and IL-7. These cytokines have been shown to be capable of stimulating osteoclast activity and bone resorption through regulating the RANKL/RANK/OPG pathway. To determine how dietary fat might affect bone metabolism, we examined in vitro bone formation, blood markers of bone homeostasis, and bone structure in male C57BL/6 mice fed either a high-fat diet (HFD, 45% kcal as fat) or a normal fat control diet (NFD, 10%) for 14 weeks starting at 6 wk of age. Cancellous bone volume/total volume ratio decreased (P<0.05) in mice fed the HFD despite a greater average body weight (10 g) than those fed the NFD (P<0.01). Compared with mice fed the NFD, the numbers of colony forming units (CFU)-fibroblastic and CFU-alkaline phosphatase positive at d 14 and mineralization nodule at d 28 were higher in bone marrow stromal cells from mice fed the HFD. Serum osteocalcin was lower (P<0.05) with HFD as compared to NFD (71.2±11.7 vs 53.4±17.0 for NFD and HFD groups, respectively). Serum TRAP and OPG levels were higher in the HFD mice when compared to the NFD mice (TRAP: 1.74±0.33 vs 2.54±1.03 U/L; OPG: 1.39±0.58 vs 2.81±2.09ng/ml, for NFD and HFD diet respectively). No significant differences were observed between the two groups for serum RANKL (3.07±2.30 vs 3.87±2.52 nmol/ml for NFD and HFD, respectively). Taken together, our data suggest that a HFD results in elevated bone resorption that exceeds increased bone formation and obesity induced by high fat intake is detrimental to bone structure.