Clinical evidence indicates that fat is inversely proportional to bone mass in elderly obese women. However, it remains unclear whether
obesity accelerates bone loss. In this report we present evidence that increased visceral fat leads to
inflammation and subsequent bone loss in 12-month-old C57BL/6J mice that were fed 10%
corn oil (CO)-based diet and a control lab chow (LC) for 6 months. As expected from our previous work, CO-fed mice demonstrated increased visceral fat and enhanced total body fat mass compared to LC. The adipocyte-specific PPARγ and bone marrow (BM) adiposity were increased in CO-fed mice. In correlation with those modifications, inflammatory
cytokines (IL-1β, IL-6, TNF-α) were significantly elevated in CO-fed mice compared to LC-fed mice. This inflammatory BM microenvironment resulted in increased
superoxide production in osteoclasts and undifferentiated BM cells. In CO-fed mice, the increased number of osteoclasts per trabecular bone length and the increased osteoclastogenesis assessed ex-vivo suggest that CO diet induces
bone resorption. Additionally, the up-regulation of osteoclast-specific
cathepsin k and RANKL expression and down-regulation of osteoblast-specific RUNX2/Cbfa1 supports this
bone resorption in CO-fed mice. Also, CO-fed mice exhibited lower trabecular bone volume in the distal femoral metaphysis and had reduced OPG expression. Collectively, our results suggest that increased
bone resorption in mice fed a CO-enriched diet is possibly due to increased
inflammation mediated by the accumulation of adipocytes in the BM microenvironment. This
inflammation may consequently increase osteoclastogenesis, while reducing osteoblast development in CO-fed mice.