Regulation of adipose tissue development and energy metabolism by VEGFB isoforms

Obesity is caused by imbalanced energy intake and expenditure. Excessive energy intake and storage in adipose tissues are associated with many diseases. Several studies have demonstrated that vascular growth endothelial factor B (VEGFB) deficiency induces obese phenotypes. However, the roles of VEGFB isoforms VEGFB 167 and VEGFB 186 in adipose tissue development and function are still not clear. In this study, genetic mouse models of adipose-specific VEGFB 167 and VEGFB 186 overexpression (aP2- Vegfb 167 tg/+ and aP2- Vegfb 186 tg/+ ) were generated and their biologic roles were investigated. On regular chow, adipose-specific VEGFB 186 is negatively associated with white adipose tissues (WATs) and positively regulates brown adipose tissues (BATs). VEGFB 186 upregulates energy metabolism and metabolism-associated genes. In contrast, VEGFB 167 has a nominal role in adipose development and function. On high-fat diet, VEGFB 186 expression can reverse the phenotypes of VEGFB deletion. VEGFB 186 overexpression upregulates BAT-associated genes and downregulates WAT-associated genes. VEGFB 186 and VEGFB 167 have very distinct roles in the regulation of adipose development and energy metabolism. As a key regulator of adipose tissue development and energy metabolism, VEGFB 186 may be a target for obesity prevention and treatment.