Regulation of hepatic lipogenesis by the transcription factor XBP1
Regulation of hepatic lipogenesis by the transcription factor XBP1
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DOI：
10.1126/science.1158042
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发表时间：
2008-06-13
期刊：
影响因子：
56.9
通讯作者：
Glimcher, Laurie H.
中科院分区：
文献类型：
--
作者：
Lee, Ann-Hwee;Scapa, Erez F.;Glimcher, Laurie H.
饮食碳水化合物通过控制糖酵解和脂肪生成途径中关键酶的表达来调节肝脂肪生成。我们发现，肝脏中正常脂肪酸合成的无关功能需要转录因子XBP1是展开蛋白反应的关键调节剂。喂食碳水化合物后，XBP1蛋白表达升高，并与诱导参与脂肪酸合成的关键基因相对应。 XBP1在肝脏中的诱导性缺失导致明显的低胆固醇血症和低糖性血症，其次是肝脏产生脂质的降低。该表型不伴有肝脂肪变性或蛋白质分泌功能妥协。将XBP1鉴定为脂肪生成的调节剂对人类血脂异常具有重要意义。
Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical enzymes in glycolytic and lipogenic pathways. We found that the transcription factor XBP1, a key regulator of the unfolded protein response, is required for the unrelated function of normal fatty acid synthesis in the liver. XBP1 protein expression in mice was elevated after feeding carbohydrates and corresponded with the induction of critical genes involved in fatty acid synthesis. Inducible, selective deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia, secondary to a decreased production of lipids from the liver. This phenotype was not accompanied by hepatic steatosis or compromise in protein secretory function. The identification of XBP1 as a regulator of lipogenesis has important implications for human dyslipidemias.