ARS | Publication request: Reduced bone mass in obese young rats through PPAR omega suppression of wnt/beta-catenin signaling and direct action of free fatty acids (NEFA)

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: March 15, 2010
Publication Date: April 12, 2010
Citation: Chen, J., Lazarenko, O.P., Shankar, K., Badger, T.M., Ronis, M.J. 2010. Reduced bone mass in obese young rats through PPAR omega suppression of wnt/beta-catenin signaling and direct action of free fatty acids (NEFA). Journal of Federation of American Societies for Experimental Biology. FASEB J. 24:726.2.

Technical 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 PPAR omega and AP2, and suppressed osteoblastogenic genes osteocalcin and Runx2 were observed in the HFD group, which exhibited down-regulation of beta-catenin protein, but up-regulation of PPAR gamma expression in bone (P < 0.05). Reciprocal regulation of beta-catenin and PPAR omega was observed in mesenchymal ST2 cells exposed to serum from HFD rats or treated with an artificial NEFA mixture. Transfection with PPAR gamma suppressed beta-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.