Regulation of adipose tissue development and energy metabolism by VEGFB isoforms.

Obesity is caused by imbalanced energy intake and expenditure. The excessive energy intake and storage in adipose tissues is associated with many diseases. Several studies have demonstrated that VEGFB deficiency induces obese phenotypes. However, roles of VEGFB isoforms VEGFB167 and VEGFB186 in adipose tissue development and function are still not clear. In this study, genetic mouse models of adipose-specific VEGFB167 and VEGFB186 overexpression (aP2-Vegfb167tg/+ and aP2-Vegfb186tg/+) were generated and their biologic roles were investigated. On regular chow, adipose-specific VEGFB186 is negatively associated with white adipose tissues (WAT) and positively regulates brown adipose tissues (BAT). VEGFB186 up-regulates energy metabolism and metabolism-associated genes. In contrast, VEGFB167 has nominal roles in adipose development and function. On high fat diet, VEGFB186 expression can reverse the phenotypes of VEGFB deletion. VEGFB186 overexpression up-regulates BAT-associated genes and down-regulates WAT-associated genes. VEGFB186 and VEGFB167 have very distinct roles in regulation of adipose development and energy metabolism. As a key regulator of adipose tissue development and energy metabolism, VEGFB186 may be a target for obesity prevention and treatment.