Body fat as a regulator of bone mass: Experimental evidence from animal models

Animal models have proven valuable for elucidating the effects of body fat on bone metabolism, and this review highlights recent findings relevant for better understanding the relationship between adiposity and bone mass. Genetically obese mice and rats with altered leptin signaling consistently show reduced bone mass, demonstrating that leptin deficiency can contribute directly to osteopenia; however, the effect of leptin on bone is concentration dependent, such that relatively low doses of leptin stimulate bone formation, whereas high concentrations of leptin suppress bone formation and increase bone resorption. The hyperleptinemia associated with obesity and leptin receptor downregulation is therefore likely to have a negative impact on bone modeling and adaptation. Likewise, diets high in fat and sugar have been observed to increase bone fragility and decrease the accumulation of bone mineral in growing rodents. In vitro studies reveal that increasing concentrations of glucose and lipid can inhibit osteogenic differentiation of mesenchymal stem cells (MSCs), and instead direct these precursors toward the adipocyte lineage. Taken together, the evidence from animal studies indicates that excess body fat and obesogenic diets may attenuate the accretion of skeletal mass in growing animals, suggesting that low bone mass (relative to body weight) may be a potential side-effect of pediatric obesity.