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	Haihong Zong, Michal Armoni, Chava Harel, Eddy Karnieli, Jeffrey E Pessin
Journal	American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 302 Issue 5 Pg. E532-9 (Mar 01 2012) ISSN: 1522-1555 [Electronic] United States
PMID	22185839 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Cytokines Insulin Cytochrome P-450 CYP2E1 Glucose
Topics	Adipose Tissue, White (metabolism) Animals Biological Transport Cytochrome P-450 CYP2E1 (genetics, physiology) Cytokines (blood) Diet, High-Fat (adverse effects) Fatty Liver (etiology, pathology, prevention & control) Glucose (metabolism) Glucose Intolerance (blood, etiology, prevention & control) Hyperlipidemias (blood, etiology, prevention & control) Insulin (metabolism) Insulin Resistance Liver (metabolism, pathology) Male Mice Mice, 129 Strain Mice, Knockout Molecular Targeted Therapy Muscle Fibers, Skeletal (metabolism) Obesity (etiology, metabolism, physiopathology, prevention & control) Signal Transduction

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