匹格列酮对肥胖小鼠棕色脂肪功能的影响
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国家自然科学基金青年项目(30900504)


Effects of pioglitazone on brown adipose tissue in mice with diet-induced obesity
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    摘要:

    目的:使用高脂饮食诱导(high fat diet-induced, HFD)的肥胖小鼠模型,研究过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor γ,PPARγ)激动剂匹格列酮(pioglitazone,PGZ)对肥胖小鼠棕色脂肪组织功能的影响,及可能的作用机制-方法:建立HFD肥胖小鼠模型(n=30);肥胖小鼠随机分为PGZ灌胃组和对照组(每组15只),PGZ 10 mg/(kg·d)灌胃1个月,对照组使用等量生理盐水灌胃-检测灌胃组及对照组小鼠的体重-口服葡萄糖耐量(OGTT)-血胰岛素含量;使用RT-PCR检测小鼠棕色脂肪组织特异性基因表达;使用Western blot检测小鼠棕色脂肪组织UCP-1蛋白的表达量-结果:PGZ灌胃的肥胖小鼠棕色脂肪功能相关基因和蛋白表达提高;PGZ灌胃组小鼠体重-血胰岛素含量和口服葡萄糖耐量改善-结论:PGZ通过调节棕色脂肪功能基因表达提高棕色脂肪功能,可能是PGZ改善胰岛素抵抗和机体代谢的重要原因-

    Abstract:

    Objective:To explore the mechanism of pioglitazone(PGZ)on brown adipose tissue(BAT)function in insulin resistance and type 2 diabetes mellitus, by using high fat diet-induced obesity(HFD)mouse. Methods:The C57BL/6J mice were randomly divided into the normal diet group and high-fat diet(HFD)group. After 20 weeks,the HFD group mice were randomly divided into obese control group and PGZ treatment group.They were orally administered placebo and PGZ[10 mg/(kg·d)]respectively for one month. The levels of body weight,serum insulin and oral glucose tolerance were measured by Biochemistry technology; The effect of pioglitazone on brown adipose tissue(BAT)was assessed by real-time quantitative PCR and Western-blot. Results:The bodyweight, serum insulin levels increased(P < 0.05)and oral glucose tolerance decreased in HFD group. Comparing to obese controls,serum insulin,glucose levels significantly decreased(P < 0.05),and oral glucose tolerance increased in PGZ treatment group; The expressions of proteins and mRNA relative to BAT function increased in PGZ treatment group. Conclusion:PGZ can enhance the function of BAT by regulating BAT relative gene and protein expressions, and may be the important reason of improving insulin resistance and metabolism in HFD mouse.

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胡 淼,刘 娟,王 龙,吕 珊,丁国宪.匹格列酮对肥胖小鼠棕色脂肪功能的影响[J].南京医科大学学报(自然科学版),2011,(5):689-693

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  • 收稿日期:2010-11-29
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