title: Cytochrome P-450 CYP2E1 knockout mice are protected against high-fat diet-induced obesity and insulin resistance.
abstract: Conventional (whole body) CYP2E1 knockout mice displayed protection against high-fat diet-induced weight gain, obesity, and hyperlipidemia with increased energy expenditure despite normal food intake and spontaneous locomotor activity. In addition, the CYP2E1 knockout mice displayed a marked improvement in glucose tolerance on both normal chow and high-fat diets. Euglycemic-hyperinsulinemic clamps demonstrated a marked protection against high-fat diet-induced insulin resistance in CYP2E1 knockout mice, with enhanced adipose tissue glucose uptake and insulin suppression of hepatic glucose output. In parallel, adipose tissue was protected against high-fat diet-induced proinflammatory cytokine production. Taken together, these data demonstrate that the CYP2E1 deletion protects mice against high-fat diet-induced insulin resistance with improved glucose homeostasis in vivo.
authors.affiliation: Dept. of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Haihong
authors.initials: H
authors.lastname: Zong
authors.forename: Michal
authors.initials: M
authors.lastname: Armoni
authors.forename: Chava
authors.initials: C
authors.lastname: Harel
authors.forename: Eddy
authors.initials: E
authors.lastname: Karnieli
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Pessin
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D006949:Hyperlipidemias / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D007328:Insulin; D019392:Cytochrome P-450 CYP2E1; D005947:Glucose