Bone Morphogenetic Proteins in Obesity Management: Therapeutic Potential and Challenges Beyond the Skeleton

Bone morphogenetic proteins (BMPs) are bone-derived osteokines that regulate energy metabolism and combat obesity by promoting brown adipocyte differentiation. BMP4, BMP7, BMP8B, and BMP9 are highly expressed in osteoblasts and bone matrix, from which they are released into circulation. They act as endocrine factors that induce brown adipogenesis, increase mitochondrial biogenesis, and increase thermogenesis via conserved signaling pathways (Smad, MAPK, and PGC1α). Concurrently, these BMPs maintain skeletal homeostasis and mediate crosstalk between bone and metabolic organs, including adipose tissue and the hypothalamus, thereby regulating appetite and energy balance. Preclinical studies have confirmed that BMP-based interventions can increase energy expenditure, improve insulin sensitivity, and alleviate obesity-related complications. However, clinical translation remains hindered by adverse effects, short half-lives, and obesity-induced BMP resistance. This review first elucidates the peripheral and central regulatory mechanisms of BMPs in energy metabolism, clarifies the subtype-specific metabolic effects of major BMPs, further evaluates their therapeutic potential against obesity and metabolic syndrome, and finally analyzes the core obstacles to clinical implementation and corresponding solution strategies.