Potential roles of bone morphogenetic protein-9 in glucose and lipid homeostasis

Bone morphogenetic protein-9 (BMP-9) is a novel cytokine which is cloned from the fetal mouse liver cDNA library and belongs to the member of the transforming growth factor-beta (TGF-beta) superfamily. BMP-9 is mainly secreted by the liver and exerts a variety of physiological functions. In this review, we present the latest knowledge on the biochemistry of BMP-9 and its role in glucose metabolism and lipid homeostasis. We introduced the expression site, structure, synthesis, and secretion of BMP-9, as well as BMP-9 signaling pathway. We also discuss the effects of BMP-9 on glucose metabolism and lipid metabolism in different organs. BMP-9 can regulate glucose and lipid homeostasis in the body by inhibiting liver gluconeogenesis, transforming white adipose tissue to brown adipose tissue, promoting muscle glycogen synthesis, increasing the uptake and utilization of glucose by muscle tissue, increasing liver and adipose tissue insulin sensitivity, promoting insulin synthesis and secretion, inhibiting liver lipid deposition, and playing a leptin-like role. Finally, through the results of animal intervention studies and human clinical studies in the review, we deeply understand the association of BMP-9 with obesity, insulin resistance (IR), type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD), which provides new ideas for the prevention and treatment of diseases.