PMID- 10049703 OWN - NLM STAT- MEDLINE DCOM- 19990311 LR - 20220409 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 255 IP - 2 DP - 1999 Feb 16 TI - Altered expression of hepatic CYP2E1 and CYP4A in obese, diabetic ob/ob mice, and fa/fa Zucker rats. PG - 300-6 AB - Hepatic levels of the cytochrome P450 (CYP) proteins 2E1 and 4A are often increased in obesity, diabetes and fasting. In such states of nutritional imbalance, CYPs 2E1 and 4A may play a more significant role in fatty acid oxidation. In order to more fully characterize the regulation of CYP2E1 and CYP4A in obesity and obesity-related (type II) diabetes, we analyzed the hepatic expression of CYP2E1 and CYP4A in ob/ob mice which are leptin deficient, and fa/fa Zucker rats which have defective leptin receptor function. CYP2E1 protein and mRNA were either unchanged or reduced in both models. Conversely, expression of murine Cyp4a10 and 4a14 in the obese mice, and 4A2 in the male fatty Zucker rat, were greatly increased. The levels of other CYP4As were either unchanged or reduced. These results show that CYP2E1 is not inevitably increased by obesity and diabetes and indicate differential regulation of CYP4A subfamily genes in rodent models. Further, they implicate leptin receptor signaling as a factor that may modulate expression of CYP gene products involved in fatty acid oxidation. CI - Copyright 1999 Academic Press. FAU - Enriquez, A AU - Enriquez A AD - Department of Medicine, University of Sydney, Westmead Hospital, New South Wales, Australia. FAU - Leclercq, I AU - Leclercq I FAU - Farrell, G C AU - Farrell GC FAU - Robertson, G AU - Robertson G LA - eng PT - Journal Article PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 9035-51-2 (Cytochrome P-450 Enzyme System) RN - EC 1.- (Mixed Function Oxygenases) RN - EC 1.14.13.- (Cytochrome P-450 CYP2E1) RN - EC 1.14.15.3 (Cytochrome P-450 CYP4A) RN - H0DE420U8G (Chlorzoxazone) SB - IM MH - Animals MH - Chlorzoxazone/metabolism MH - Cytochrome P-450 CYP2E1/*biosynthesis/genetics MH - Cytochrome P-450 CYP4A MH - Cytochrome P-450 Enzyme System/*biosynthesis/genetics MH - Diabetes Mellitus/*enzymology/genetics/physiopathology MH - Female MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Obese MH - Microsomes, Liver/*enzymology MH - Mixed Function Oxygenases/*biosynthesis/genetics MH - *Obesity MH - Rats MH - Rats, Zucker MH - Sex Factors EDAT- 1999/03/02 00:00 MHDA- 1999/03/02 00:01 CRDT- 1999/03/02 00:00 PHST- 1999/03/02 00:00 [pubmed] PHST- 1999/03/02 00:01 [medline] PHST- 1999/03/02 00:00 [entrez] AID - S0006-291X(99)90202-4 [pii] AID - 10.1006/bbrc.1999.0202 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1999 Feb 16;255(2):300-6. doi: 10.1006/bbrc.1999.0202.