Cold‐induced expression of the VEGF gene in brown adipose tissue is independent of thermogenic oxygen consumption

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Abstract
To examine whether cold‐induced vascular endothelial growth factor (VEGF) gene expression in brown adipose tissue involved generation of hypoxic oxygen levels by thermogenic processes, we cold‐exposed wild‐type mice, as well as uncoupling protein‐1 (UCP1)‐ablated mice in which no thermogenesis in brown adipocytes can be induced. Cold exposure stimulated VEGF expression in both wild‐type and UCP1‐ablated mice. Unexpectedly, the effect was 3‐fold higher in UCP1‐ablated animals, whereas cultured brown adipocytes from both genotypes responded identically to norepinephrine stimulation. These results demonstrate that generation of low oxygen levels does not contribute to cold‐induced VEGF expression in brown adipose tissue, but the results are consistent with an adrenergic regulation of expression.