Cytochrome P450 2E1 (CYP2E1) positively regulates lipid catabolism and induces browning in 3T3-L1 white adipocytes

Abstract

AimsBrowning induction (beiging) of white adipocytes is an emerging prospective strategy to defeat obesity and its related metabolic disorders. Cytochrome P450 2E1 (CYP2E1), a membrane protein which belongs to the cytochrome P450 superfamily, reportedly functions in the xenobiotic metabolism in the body, especially ethanol metabolism. Although previous studies have reported the effect of CYP2E1 on obesity in animal models, the data remains controversial. In the current study, we investigate for the first time, the role of CYP2E1 in lipid metabolism in 3T3-L1 white adipocytes, with a focus on fat browning. Methods3T3-L1 white adipocytes and Cyp2e1 siRNA were applied to investigate the role of CYP2E1 in white adipocytes. After that, cells were seperately exposed to β3-AR agonist, β3-AR antagonist and p38 inhibitor to identify the pathway which CYP2E1 was involved in to regulate browning event in white adipocytes. Key findingsWe found that CYP2E1 deficiency results in reduced adipogenesis and lipogenesis as well as brown adipocyte-like phenotype induction. A mechanistic study to identify the molecular signals for CYP2E1 regulation in the browning of white adipocytes revealed that CYP2E1 inhibition deters the β3-adrenergic receptor activation and its downstream targets. SignificanceOur data unveilved a previously unknown mechanism in the regulation of browning by CYP2E1 in 3T3-L1 white adipocytes, suggesting that CYP2E1 is a promising molecular target for the treatment of obesity and its related diseases.