能量限制对小鼠胰岛素抵抗与炎症的作用及其机制

IMPROVEMENT OF INSULIN RESISTANCE AND INFLAMMATION BY CALORIE RESTRICTION IN MICE AND POSSIBLE MECHANISMS

目的 通过对小鼠食物的能量限制(caloricrestriction,CR),研究能量限制对小鼠胰岛素敏感性和炎症的作用及其机制。方法 8w龄的雄性C57BL/6J小鼠随机分为对照组(C57 CON,n=10)和能量限制组(C57 CR,n=12),8w龄的雄性db/db小鼠随机分为对照组(db CON,n=10)和能量限制组(db CR,n=12),能量限制水平皆为小鼠正常能量摄入量的50%,而矿物质、维生素等营养素的摄入量维持正常水平。C57BL/6J小鼠和db/db小鼠分别干预2w和3w后,测定口服糖耐量和胰岛素耐量。对小鼠实行安乐死,取血和肝脏组织。采用酶联免疫吸附试剂盒(ELISA)检测各组小鼠血清甘油三脂(TG)、总胆固醇(TC)以及肿瘤坏死因子-α (tumor necrosis factor-α,TNF-α)水平;采用免疫印迹检测肝脏组织中与胰岛素敏感性相关蛋白的表达变化情况。结果 与正常对照组比较,能量限制可以显著降低空腹血糖、胰岛素水平以及糖耐量和胰岛素抵抗指数(P<0.05),降低血清甘油三脂(TG)、总胆固醇(TC)水平(P<0.05),显著刺激AMPK、SIRT-1、PPAR-γ的表达和AKT的磷酸化水平(P<0.05),并显著降低db/db小鼠血清IL-6和IL-1β水平(P<0.01)。结论 一定程度能量限制可以改善小鼠胰岛素敏感性,并降低小鼠炎症。[营养学报,2022,44(5):473-478,483]

Objective To study the effects of calorie restriction(CR) on insulin sensitivity and inflammation in mice.Methods Eight-week-old male C57BL/6J and db/db mice were randomly divided into control group(C57 CON, n=10) and caloric restriction group(C57 CR, n=12). The energy restriction was conducted by providing 50% of the normal energy intake of the mice, while the intakes of minerals, vitamins and other nutrients were maintained at normal levels. Oral glucose tolerance and insulin tolerance were measured in C57BL/6J and db/db mice after 2 or 3 weeks of intervention, respectively.The mice were euthanized and blood and liver tissues were taken. The enzyme-linked immunosorbent kit(ELISA) was used to detect serum levels of triglycerides(TG), total cholesterol(TC), and tumor necrosis factor-α(TNF-α). Western blotting was used to detect the expressions of proteins related to insulin sensitivity. Results Compared with the normal control group,energy restriction significantly reduced fasting blood glucose, insulin, glucose tolerance, insulin resistance(P<0.05), serum triglycerides(TG) and total cholesterol(TC)(P<0.05), stimulated the expressions of AMPK, SIRT-1, PPAR-γ and phosphorylation level of AKT(P<0.05) in the liver, and decreased serum IL-6 and IL-1β in db/db mice(P<0.01).Conclusion Caloric restriction can improve insulin sensitivity and reduce inflammation to some extent in mice. [ACTA NUTRIMENTA SINICA, 2022,44(5):473-478,483]