Deletion of PPARγ in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance
Deletion of PPARγ in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance
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DOI：
10.1073/pnas.0306743102
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发表时间：
2005-04-26
影响因子：
11.1
通讯作者：
Magnuson, MA
中科院分区：
文献类型：
--
作者：
Jones, JR;Barrick, C;Magnuson, MA
过氧化物酶体增殖物激活受体γ(PPARγ)在脂肪细胞分化、糖代谢等生理过程中发挥重要作用。为了进一步探索PPARγ在脂肪组织中的作用，我们使用了Cre/loxP策略来产生脂肪特异性的PPARγ基因敲除小鼠。这些动物在棕色和白色脂肪组织的形成和功能上都表现出明显的异常。当喂食高脂饮食时，脂肪特异性PPAR伽马基因敲除小鼠尽管吞噬过度，但体重增加减少，血清瘦素和脂联素浓度降低，并且没有出现葡萄糖耐受或胰岛素抵抗。体内葡萄糖动力学的特征表明，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。我们的发现进一步说明了PPAR-γ在脂肪组织发育中的重要作用，并提示肝脏PPAR-γ的代偿性诱导可能刺激肝脏葡萄糖处置的增加。
Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a crucial role in adipocyte differentiation, glucose metabolism, and other physiological processes. To further explore the role of PPAR gamma in adipose tissues, we used a Cre/loxP strategy to generate adipose-specific PPAR gamma 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 PPAR gamma 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 PPAR gamma in the development of adipose tissues and suggest that a compensatory induction of hepatic PPAR gamma may stimulate an increase in glucose disposal by the liver.