Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver
Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver
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DOI：
10.1016/j.cmet.2004.11.004
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发表时间：
2005-01-01
期刊：
影响因子：
29
通讯作者：
Brown, MS
中科院分区：
文献类型：
--
作者：
Kuriyama, H;Liang, GS;Brown, MS
护送蛋白SCAP将SREBP从ER转运到高尔基体，在高尔基体释放活性结构域以激活脂肪酸（FA）和胆固醇合成的基因。肝脏中具有条件性SCAP缺陷（L-Scap（-））的小鼠表现出肝脏脂质合成的显著减少。在这里，我们表明，减少脂肪酸合成的肝脏是平衡的同等增加非肝组织，主要是脂肪组织。脂肪酸的肝外合成保留了脂肪量，即使L-Scap（-）小鼠食用无脂肪饮食。这种代偿性反应在禁食后消失，暗示了胰岛素的作用，胰岛素是FA合成的主要激素激活剂。这种反应由脂肪细胞SREBP-1c及其靶mRNA的胰岛素依赖性增加介导。在L-Scap（-）小鼠的附睾脂肪中，磷酸化Akt、Glut-4 mRNA和葡萄糖摄取也增加，表明胰岛素超敏反应。在L-Scap（-）小鼠中，血浆VLDL甘油三酯显著降低，强调了在脂肪而不是肝脏中合成FA的益处。
The escort protein SCAP transports SREBPs from ER to Golgi where the active domains are released to activate genes for fatty acid (FA) and cholesterol synthesis. Mice with conditional SCAP deficiency in liver (L-Scap(-)) manifest marked reductions in hepatic lipid synthesis. Here, we show that the decreased FA synthesis in liver is balanced by an equal increase in nonhepatic tissues, primarily adipose tissue. Extrahepatic synthesis of FAs preserves adipose mass, even when L-Scap(-) mice consume a fat-free diet. This compensatory response disappears upon fasting, implicating a role for insulin, the major hormonal activator of FA synthesis. This response is mediated by an insulin-dependent increase in adipocyte SREBP-1c and its target mRNAs. In epididymal fat of L-Scap(-) mice, phosphorylated Akt, Glut-4 mRNA, and glucose uptake are also increased, indicating insulin hypersensitivity. Plasma VLDL triglycerides are dramatically reduced in L-Scap(-) mice, underscoring the benefits of synthesizing FAs in fat rather than liver.