Reduced bone mass in obese young rats through PPARγ suppression of Wnt/β‐catenin signaling and direct action of free fatty acids (NEFA)

Abstract

The relationship of obesity to skeletal development is unclear. We utilized total enteral nutrition to feed high and low fat diets (HFD and LFD) to rats for 4 wks to produce obesity. Weight gain was matched but fat mass, serum leptin and NEFA were increased by HFD (P<0.05). HFD lowered total bone mineral content and density (P<0.05) accompanied by decreased serum osteocalcin and increases in resorption marker RatLaps. Increased bone marrow adiposity and adipogenic genes PPARγ and AP2, and suppressed osteoblastogenic genes osteocalcin and Runx2 were observed in the HFD group which exhibited down‐regulation of β‐catenin protein, but up‐regulation of PPARγ expression in bone (P<0.05). Reciprocal regulation of β‐catenin and PPARγ was observed in mesenchymal ST2 cells exposed to serum from HFD rats or treated with an artificial NEFA mixture. Transfection with PPARγ suppressed β‐catenin signaling. These data suggest NEFA directly stimulates bone marrow adipogenesis while suppressing bone formation. These effects of HFD may impair attainment of peak bone mass and increase risk of osteoporosis later in life. USDA CRIS‐6251‐51000‐007‐03S.