The effect of hypoxia inducible factors on brown adipose tissue thermogenesis

Abstract

Systemic energy imbalance between energy intake and expenditure lies at the center of obesity pandemic. Brown adipocyte plays an important role in increasing energy expenditure by generating heat. Hypoxia-inducible factor (HIF) regulates the expression of glucose transporter 1 and several glycolytic enzymes, however its role in brown adipose tissues has not been elucidated, yet. There are two major isoforms of HIF in adipocytes, HIF1α and HIF2α. Here, I studied the mechanism of how HIF1α regulates cold-induced thermogenesis in brown adipocytes. HIF1α expression was increased in brown adipose tissue after cold exposure. Moreover, β adrenergic receptor agonist treatment increased HIF1α expression in brown adipocytes in vitro. HIF1α knockdown decreased isoproterenol- induced UCP1 expression. On the other hand, I found that HIF2α is involved in brown pre-adipocyte differentiation. These results suggest that HIF1α and HIF2α can modulate adaptive thermogenesis in brown adipose tissue.