诱导成纤维细胞生长因子 21 的产生并不需要激活小鼠肝脏 X 盒结合蛋白 1。
Induction of fibroblast growth factor 21 does not require activation of the hepatic X-box binding protein 1 in mice.
机构信息
Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
出版信息
Mol Metab. 2017 Dec;6(12):1616-1624. doi: 10.1016/j.molmet.2017.09.006. Epub 2017 Oct 5.
OBJECTIVE
Fibroblast growth factor 21 (FGF21), a key regulator of the metabolic response to fasting, is highly induced by endoplasmic reticulum (ER) stress. The X-box binding protein 1 (Xbp1) is one of several ER stress proteins that has been shown to directly activate the FGF21 promoter. We aimed to determine whether hepatic Xbp1 is required for induction of hepatic FGF21 in vivo.
METHODS
Mice bearing a hepatocyte-specific deletion of Xbp1 (Xbp1) were subjected to fasting, pharmacologic ER stress, or a ketogenic diet, all potent stimuli of Fgf21 expression.
RESULTS
Hepatocyte-specific Xbp1 knockout mice demonstrated normal induction of FGF21 in response to fasting or pharmacologic ER stress and enhanced induction of FGF21 in response to a ketogenic diet. Consistent with preserved induction of FGF21, Xbp1 mice exhibited normal induction of FGF21 target genes and normal ketogenesis in response to fasting or a ketogenic diet.
CONCLUSION
Hepatic Xbp1 is not required for induction of FGF21 under physiologic or pathophysiologic conditions in vivo.
目的
成纤维细胞生长因子 21（FGF21）是一种调节饥饿状态下代谢反应的关键因子，其表达受到内质网（ER）应激的强烈诱导。X 盒结合蛋白 1（Xbp1）是几种 ER 应激蛋白之一，已被证明可直接激活 FGF21 启动子。我们旨在确定肝脏 Xbp1 是否是体内诱导肝脏 FGF21 所必需的。
方法
使用肝细胞特异性 Xbp1 敲除（Xbp1）小鼠，对其进行禁食、药物性 ER 应激或生酮饮食处理，这些均是 Fgf21 表达的有效刺激物。
结果
肝细胞特异性 Xbp1 敲除小鼠在禁食或药物性 ER 应激时 FGF21 的诱导正常，而生酮饮食时 FGF21 的诱导增强。与 FGF21 的诱导正常一致，Xbp1 小鼠在禁食或生酮饮食时 FGF21 靶基因的诱导和酮体生成正常。
结论
在体内生理或病理条件下，肝脏 Xbp1 不是诱导 FGF21 所必需的。
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