Cytochrome P-450 CYP2E1 knockout mice are protected against high-fat diet-induced obesity and insulin resistance

Haihong Zong, Michal Armoni, Chava Harel, Eddy Karnieli, Jeffrey E. Pessin

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Conventional (whole body) CYP2E1 knockout mice displayed protection against high-fat dietinduced 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.

Original languageEnglish (US)
Pages (from-to)E532-E539
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5
Publication statusPublished - Mar 1 2012

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