Body Fat as a Regulator of Bone Mass: Experimental Evidence from Animal Models

Abstract

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.

Genetic variations and physical activity as determinants of limb bone morphology: An experimental approach using a mouse model

“…Mice are widely considered appropriate models for addressing questions about human bone biology (Beamer et al, 2002; Forwood, 2008; Hamrick et al, 2009; Gross et al, 2010), because the genes and molecular pathways affecting the skeleton are highly conserved in the mouse and human (Karsenty, 2003). Nevertheless, major differences exist between mice and humans and the impact of these differences on experimental data is currently unknown.…”

The role of nutrient partitioning and stem cell differentiation in pediatric obesity: a new theory

“…For example, in growing rodents, diets high in fat and sugar tend to decrease the accumulation of bone mineral; moreover, in vitro studies have found that increasing concentrations of glucose and lipid can inhibit differentiation of mesenchymal stem cells into bone, and instead direct these precursors toward the adipocyte lineage. Taken together, the evidence from animal studies indicates that obesogenic diets may attenuate the accretion of skeletal mass in growing animals (33). Perhaps epidemiologic level studies in humans have failed to demonstrate relations between diet composition and body fatness because of the difficulty of measuring free‐living diet with sufficient precision.…”

A Role for Myokines in Muscle-Bone Interactions

“…These factors include leptin and adiponectin, as well as inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (11, 12). Despite the fact that muscle is the largest internal organ in the body, and muscle also secretes a variety of different cytokines and growth factors collectively referred to as “myokines”, a role for muscle-derived factors in health and disease is only recently being appreciated (28, 34).…”