PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance
PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance
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DOI：
10.1016/s1097-2765(00)80210-5
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发表时间：
1999-10-01
期刊：
影响因子：
16
通讯作者：
Kadowaki, T
中科院分区：
文献类型：
--
作者：
Kubota, N;Terauchi, Y;Kadowaki, T
已知激动剂诱导的过氧化物酶体增殖物激活受体γ（PPARγ）激活可引起脂肪细胞分化和胰岛素敏感性。通过基因靶向研究 PPAR γ 的生物学作用。纯合 PPAR γ 缺陷胚胎在 10.5-11.5 dpc 时因胎盘功能障碍而死亡。出乎意料的是，杂合 PPAR γ 缺陷小鼠在高脂肪饮食下免受由于脂肪细胞肥大而导致的胰岛素抵抗的发展。 PPAR γ 激动剂治疗消除了这些表型。尽管脂肪细胞较小且脂肪量减少，但杂合 PPAR γ 缺陷小鼠仍表现出瘦素的过度表达和分泌过多，这至少可以部分解释这些表型。这项研究揭示了 PPAR γ 在由于脂肪细胞肥大和胰岛素抵抗而导致的高脂肪饮食引起的肥胖中发挥着迄今为止无法预测的作用，这需要 PPAR γ 的两个等位基因。
Agonist-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPAR gamma was investigated by gene targeting. Homozygous PPAR gamma-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPAR gamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPAR gamma agonist treatment. Heterozygous PPAR gamma-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPAR gamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPAR gamma.