Impact of obesity on bone integrity and mesenchymal stem cell activity in Ossabaw swine

Abstract

Ossabaw swine are an exciting model to study the effects of diet induced obesity. We examined the affects of an obesigenic diet on bone integrity and on mesenchymal stem cells (MSC) activity, which underpins bone integrity. Pigs fed an obesigenic diet had greater (P < 0.05) body fat % and insulin resistance. Obese pigs had larger and heavier bones (P < 0.05), however the percentage of mineral in the bone did not differ between obese and lean pigs. In order to evaluate alterations in MSC activity, MSC from obese and lean pigs were cultured under adipocytic and osteogenic conditions. Under osteogenic conditions, the expression of genes indicative of osteoblastic differentiation (RunX2 and osteocalcin) were greater (P<0.1) in MSC isolated from obese pigs. Under adipogenic conditions, increased gene expression of markers of adipocytic differentiation (PPARG, AP2, and LPL), as well as greater lipid accumulation (Oil Red O staining), were seen in MSC isolated from the lean pigs. While the increased osteogenic activity of MSC from obese pigs supports the bone data, the reduced adipogenic activity of these cells seems counterintuitive. However, the reduced in vitro adipocytic differentiation of MSC from obese pigs may be a result of the insulin resistance seen in these pigs. These results suggest that obesity and insulin resistance may have long‐term effects on bone development and MSC activity.