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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipose Tissue, White / metabolism
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Animals
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Biological Transport
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Cytochrome P-450 CYP2E1 / genetics
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Cytochrome P-450 CYP2E1 / physiology*
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Cytokines / blood
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Diet, High-Fat / adverse effects*
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Fatty Liver / etiology
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Fatty Liver / pathology
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Fatty Liver / prevention & control
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Glucose / metabolism
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Glucose Intolerance / blood
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Glucose Intolerance / etiology
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Glucose Intolerance / prevention & control
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Hyperlipidemias / blood
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Hyperlipidemias / etiology
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Hyperlipidemias / prevention & control
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Insulin / metabolism
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Insulin Resistance*
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Liver / metabolism
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Liver / pathology
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Male
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Mice
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Mice, 129 Strain
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Mice, Knockout
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Molecular Targeted Therapy
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Muscle Fibers, Skeletal / metabolism
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Obesity / etiology
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Obesity / metabolism*
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Obesity / physiopathology
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Obesity / prevention & control
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Signal Transduction
Substances
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Cytokines
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Insulin
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Cytochrome P-450 CYP2E1
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Glucose