Cha Dae Ryong, Han Jee Young, Su Dong Ming, Zhang Yahua, Fan Xuefeng, Breyer Matthew D, Guan Youfei
Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn. 37232-2372, USA.
Am J Nephrol. 2007;27(5):479-82. doi: 10.1159/000106485. Epub 2007 Jul 25.
BACKGROUND/AIMS: Insulin resistance is a central feature of the metabolic syndrome and progressively increases with age, resulting in excessively high incidence of type II diabetes in the elderly population. Peroxisome proliferator-activated receptor-alpha (PPARalpha) is widely expressed in insulin target tissues, including those of the liver, kidney, and muscle, where it mediates expression of genes promoting fatty acid beta-oxidation. The aim of this study was to evaluate the potential role of PPARalpha in insulin resistance in aging mice induced by a high-fat diet.
We used male PPARalpha knockout (KO) mice and wild-type (WT) littermates that were 18 months old. Animals were fed with a high-fat diet (HFD) for 4 weeks, and metabolic parameters associated with insulin sensitivity were assessed.
Following HFD treatment, WT mice showed more severe insulin resistance than did mice lacking the PPARalpha gene, as assessed by both the glucose tolerance test (GTT) and insulin tolerance test (ITT). In addition, WT mice exhibited significantly higher HOMA-IR, plasma total cholesterol levels and urinary albumin-creatinine ratio but less liver weight than did PPARalpha KO mice.
These data suggest that PPARalpha gene deficiency may protect aged mice from developing insulin resistance and albuminuria induced by a HFD.
背景/目的：胰岛素抵抗是代谢综合征的核心特征，且随年龄增长而逐渐增加，导致老年人群中II型糖尿病的发病率过高。过氧化物酶体增殖物激活受体α（PPARα）在胰岛素靶组织中广泛表达，包括肝脏、肾脏和肌肉组织，在这些组织中它介导促进脂肪酸β氧化的基因的表达。本研究的目的是评估PPARα在高脂饮食诱导的衰老小鼠胰岛素抵抗中的潜在作用。
我们使用了18个月大的雄性PPARα基因敲除（KO）小鼠和野生型（WT）同窝小鼠。动物喂食高脂饮食（HFD）4周，并评估与胰岛素敏感性相关的代谢参数。
通过葡萄糖耐量试验（GTT）和胰岛素耐量试验（ITT）评估，高脂饮食处理后，野生型小鼠比缺乏PPARα基因的小鼠表现出更严重的胰岛素抵抗。此外，与PPARα基因敲除小鼠相比，野生型小鼠的稳态模型评估胰岛素抵抗（HOMA-IR）、血浆总胆固醇水平和尿白蛋白肌酐比值显著更高，但肝脏重量更低。
这些数据表明，PPARα基因缺陷可能保护老年小鼠免受高脂饮食诱导的胰岛素抵抗和蛋白尿的影响。
