Deletion of PPARgamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance.
Deletion of PPARgamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance.
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DOI：
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发表时间：
2005
影响因子：
11.1
通讯作者：
Julie R. Jones;C. Barrick;Kyoung-Ah Kim;J. Lindner;B. Blondeau;Y. Fujimoto;M. Shiota;R. Kesterson;B. Kahn;M. Magnuson
中科院分区：
文献类型：
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作者：
Julie R. Jones;C. Barrick;Kyoung-Ah Kim;J. Lindner;B. Blondeau;Y. Fujimoto;M. Shiota;R. Kesterson;B. Kahn;M. Magnuson
过氧化物酶体增殖物激活受体γ（PPARgamma）在脂肪细胞分化、葡萄糖代谢和其他生理过程中起着至关重要的作用。为了进一步探索PPARgamma在脂肪组织中的作用，我们使用Cre/loxP策略来产生脂肪特异性PPARgamma敲除小鼠。这些动物在棕色和白色脂肪组织的形成和功能方面均表现出明显异常。当喂食高脂饮食时，脂肪特异性PPARgamma基因敲除小鼠尽管食欲过盛，但体重增加减少，血清瘦素和脂联素浓度降低，并且没有发生葡萄糖耐受不良或胰岛素抵抗。体内葡萄糖动力学的表征指出改善肝脏葡萄糖代谢是预防高脂饮食诱导的胰岛素抵抗的基础。我们的研究结果进一步说明了PPARgamma在脂肪组织发育中的重要作用，并表明肝脏PPARgamma的代偿性诱导可能会刺激肝脏葡萄糖处置的增加。
Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a crucial role in adipocyte differentiation, glucose metabolism, and other physiological processes. To further explore the role of PPARgamma in adipose tissues, we used a Cre/loxP strategy to generate adipose-specific PPARgamma knockout mice. These animals exhibited marked abnormalities in the formation and function of both brown and white adipose tissues. When fed a high-fat diet, adipose-specific PPARgamma knockout mice displayed diminished weight gain despite hyperphagia, had diminished serum concentrations of both leptin and adiponectin, and did not develop glucose intolerance or insulin resistance. Characterization of in vivo glucose dynamics pointed to improved hepatic glucose metabolism as the basis for preventing high-fat diet-induced insulin resistance. Our findings further illustrate the essential role for PPARgamma in the development of adipose tissues and suggest that a compensatory induction of hepatic PPARgamma may stimulate an increase in glucose disposal by the liver.