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.
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Yang Chen, Xin Li, Jing Zhang, Mingjiao Zhang, Salah Adlat, Xiaodan Lu, Dan Li, Honghong Jin, Chenhao Wang, Zin Mar Oo, Farooq Hayel, Quangang Chen, Xufeng Han, Renjin Chen, Xuechao Feng, Luqing Zhang, and Yaowu Zheng
Yang Chen, Mingyue Zhao, Chenhao Wang, Huaizhen Wen, Yuntao Zhang, Mingxu Lu, Salah Adlat, Tingting Zheng, Mingjiao Zhang, Dan Li, Xiaodan Lu, Mengwei Guo, Hongyu Chen, Luqing Zhang, Xuechao Feng, and Yaowu Zheng
Excessive fat accumulation causes obesity and many diseases. Previous study demonstrates VEGFB universal knockout induces obese phenotypes including expansion of white adipose tissue, whitening of brown adipose tissue, increase of fat accumulation and reduction in energy consumption. However, roles of VEGFB in adipose tissues are not clear. In this study, we have generated a mouse model with adipose-specific VEGFB repression using CRISPR/dCas9 system (Vegfb AdipoDown ) and investigated the roles of VEGFB in adipose development and energy metabolism. VEGFB repression induced significant changes in adipose tissue structure and function. Vegfb AdipoDown mice have larger body sizes, larger volume of white adipose tissues than its wild type littermates. Adipose-specific VEGFB repression induced morphological and functional transformation of adipose tissues toward white adipose for energy storage. Metabolic processes are broadly changed in Vegfb AdipoDown adipose tissues including carbohydrate metabolism, lipid metabolism, nucleotide metabolism and amino acid metabolism. We have demonstrated that adipose VEGFB repression can recapitulate most of the phenotypes of the whole body VEGFB knockout mouse. Intriguingly, approximately 50% VEGFB repression in adipose tissues can almost completely mimic the effects of universal Vegfb deletion, suggesting adipose VEGFB is a major regulator of energy metabolism and may be important in prevention and treatment of obesity.