Insig-1 "brakes" lipogenesis in adipocytes and inhibits differentiation of preadipocytes
Insig-1 "brakes" lipogenesis in adipocytes and inhibits differentiation of preadipocytes
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DOI：
10.1073/pnas.1133426100
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发表时间：
2003-08-05
影响因子：
11.1
通讯作者：
Unger, RH
中科院分区：
文献类型：
--
作者：
Li, JP;Takaishi, K;Unger, RH
我们检查了正常小鼠在饮食引起的肥胖发病时脂肪组织中的基因表达。胰岛素诱导基因1 (insg -1) mRNA在高脂饮食中逐渐升高，在限制饮食中下降。由于insg -1与内质网中的甾醇调节元件结合蛋白结合，从而阻断甾醇调节元件结合蛋白激活所需的蛋白水解过程，因此我们测试了其对脂肪生成的影响。在3T3-L1细胞分化过程中，insg -1和-2与aP(2) mRNA平行升高。在未分化的3T3-L1前脂肪细胞中，无法检测到脂肪生成转录因子（碳水化合物反应元件结合蛋白）的mRNA，但在25 mM的分化过程中显著升高，而在5 mM的葡萄糖中则没有。将小鼠或人insg -1转染到3T3-L1前脂肪细胞中，完全阻止油红O染色，阻断aP(2)、过氧化物酶体增殖激活受体γ(2)和碳水化合物反应元件结合蛋白的上调，同时降低前脂肪细胞因子1的下调。结果表明，insg -1的表达限制了成熟脂肪细胞的脂肪生成，并阻断了前脂肪细胞的分化。
We have examined gene expression in the fat tissue of normal mice at the onset of diet-induced obesity. Insulin-induced gene 1 (insig-1) mRNA rose progressively with a high-fat diet and declined on a restricted diet. Because insig-1 binds sterol regulatory element-binding protein cleavage-activating protein in the endoplasmic reticulum, thereby blocking proteolytic processing required for sterol regulatory element-binding protein activation, we tested its influence on lipogenesis. In differentiating 3T3-L1 cells, insig-1 and -2 rose in parallel with aP(2) mRNA during differentiation. The mRNA of the lipogenic transcription factor, carbohydrate response element-binding protein, was undetectable in undifferentiated 3T3-L1 preadipocytes but rose dramatically during differentiation in 25 mM, but not in 5 mM, glucose. Transfection of mouse or human insig-1 into 3T3-L1 preadipocytes completely prevented oil red O staining and blocked upregulation of aP(2), peroxisome proliferator-activated receptor gamma(2), and carbohydrate response element-binding protein, while reducing down-regulation of preadipocyte factor 1. The results suggest that insig-1 expression restricts lipogenesis in mature adipocytes and blocks differentiation in preadipocytes.