Adipose tissue exposed to cold

Cold triggers VEGF dependent but hypoxia independent angiogenesis in adipose tissues and anti-VEGF agents modulate adipose metabolism The molecular mechanisms of angiogenesis in relation to adipose tissue metabolism remain poorly understood. Here we show that exposure of mice to cold led to conversion of white adipose tissue (WAT) to brown-like adipose tissue, accompanying the switch of an active angiogenic phenotype. Gene expression profile analysis showed VEGF was upregulated via most likely hypoxia-independent PGC-1 transcriptional activation. Intriguingly, VEGFR2 blockage abolished the cold-induced angiogenesis, significantly impaired nonshivering thermogenesis capacity, and markedly reduced adipose metabolism. Unexpectedly, VEGFR1 blockage resulted in opposite effects by increasing adipose vascularity and metabolism. These findings demonstrate that VEGFR2 and VEGFR1 mediate polarized activities in modulating adipose angiogenesis and metabolism. Taken together, our findings have conceptual implications in applying angiogenesis modulators for the treatment of obesity and metabolic disorders. Keywords: Time course Mice were exposed to cold and white addipose tissue was collected at different time points