Dept. of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Am J Physiol Endocrinol Metab. 2012 Mar 1;302(5):E532-9. doi: 10.1152/ajpendo.00258.2011. Epub 2011 Dec 20.
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.
传统(全身)CYP2E1 敲除小鼠表现出对高脂肪饮食诱导的体重增加、肥胖和高脂血症的保护作用,尽管食物摄入量和自发活动正常,但能量消耗增加。此外,CYP2E1 敲除小鼠在正常和高脂肪饮食下的葡萄糖耐量也显著改善。在给予正常血糖高胰岛素钳夹时,CYP2E1 敲除小鼠对高脂肪饮食诱导的胰岛素抵抗有明显的保护作用,表现为脂肪组织葡萄糖摄取增加,以及胰岛素抑制肝葡萄糖输出。同时,脂肪组织也免受高脂肪饮食诱导的促炎细胞因子产生的影响。总之,这些数据表明 CYP2E1 的缺失可保护小鼠免受高脂肪饮食诱导的胰岛素抵抗,改善体内葡萄糖稳态。