Altered expression of hepatic CYP2E1 and CYP4A in obese, diabetic ob/ob mice, and fa/fa Zucker rats

Hepatic levels of the cytochrome P450 (CYP) proteins 2E1 and 4A are often i ncreased in obesity, diabetes and fasting. In such states of nutritional im balance, CYPs 2E1 and 4A may play a more significant role in fatty acid oxi dation. In order to more fully characterize the regulation of CYP2E1 and CY P4A in obesity and obesity-related (type II) diabetes, we analyzed the hepa tic expression of CYP2E1 and CYP4A in ob/ob mice which are leptin deficient , and fa/fa Zucker rats which have defective leptin receptor function. CYP2 E1 protein and mRNA were either unchanged or reduced in both models. Conver sely, expression of murine CYP2E1 and 4a14 in the obese mice, and 4A2 in th e male fatty Zucker rat, were greatly increased. The levels of other CYP4As were either unchanged or reduced. These results show that CYP2E1 is not in evitably increased by obesity and diabetes and indicate differential regula tion of CYP4A subfamily genes in rodent models. Further, they implicate lep tin receptor signaling as a factor that may modulate expression of CYP gene products involved in fatty acid oxidation. (C) 1999 Academic Press.