Liver X receptors in lipid signalling and membrane homeostasis.
Liver X receptors in lipid signalling and membrane homeostasis.
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DOI：
10.1038/s41574-018-0037-x
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Tontonoz P
中科院分区：
文献类型：
--
作者：
Wang B;Tontonoz P
肝X受体α和β （LXRα和LXRβ）是核受体，在脂质代谢的转录控制中起关键作用。LXRs的转录活性在细胞胆固醇水平升高时被诱导。LXRs结合并调节与胆固醇吸收、运输、外排、排泄和转化为胆汁酸有关的蛋白质编码基因的表达。LXR通路协调的组织特异性作用维持全身胆固醇稳态并调节免疫和炎症反应。LXRs还通过控制脂肪生成转录因子固醇调节元件结合蛋白1c和调节编码脂肪酸延伸和去饱和蛋白的基因来调节脂肪酸代谢。LXRs对磷脂代谢有重要影响，磷脂和胆固醇是细胞膜的主要成分。LXR激活通过诱导溶血磷脂酰胆碱酰基转移酶3的转录，优先驱动多不饱和脂肪酸进入磷脂。LXR通路将细胞固醇水平与膜磷脂中脂肪酸的饱和偶联的能力对几个生理过程有影响，包括脂蛋白产生、膳食脂质吸收和肠道干细胞增殖。了解LXRs如何调节膜组成和功能，可能为研究与脂质代谢失调相关的疾病，包括动脉粥样硬化、糖尿病和癌症，提供新的治疗见解。
Liver X receptors α and β (LXRα and LXRβ) are nuclear receptors with pivotal roles in the transcriptional control of lipid metabolism. Transcriptional activity of LXRs is induced in response to elevated cellular levels of cholesterol. LXRs bind to and regulate the expression of genes that encode proteins involved in cholesterol absorption, transport, efflux, excretion and conversion to bile acids. The coordinated, tissue-specific actions of the LXR pathway maintain systemic cholesterol homeostasis and regulate immune and inflammatory responses. LXRs also regulate fatty acid metabolism by controlling the lipogenic transcription factor sterol regulatory element-binding protein 1c and regulate genes that encode proteins involved in fatty acid elongation and desaturation. LXRs exert important effects on the metabolism of phospholipids, which, along with cholesterol, are major constituents of cellular membranes. LXR activation preferentially drives the incorporation of polyunsaturated fatty acids into phospholipids by inducing transcription of the remodelling enzyme lysophosphatidylcholine acyltransferase 3. The ability of the LXR pathway to couple cellular sterol levels with the saturation of fatty acids in membrane phospholipids has implications for several physiological processes, including lipoprotein production, dietary lipid absorption and intestinal stem cell proliferation. Understanding how LXRs regulate membrane composition and function might provide new therapeutic insight into diseases associated with dysregulated lipid metabolism, including atherosclerosis, diabetes mellitus and cancer.
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影响因子：
4.8
作者：
Cha, Ji-Young;Repa, Joyce J.
通讯作者：
Repa, Joyce J.
DOI：
10.1073/pnas.0404297101
发表时间：
2004-08-03
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
GOLDSTEIN, JL
影响因子：
30.8
作者：
Bodzioch, M;Orsó, E;Schmitz, G
通讯作者：
Schmitz, G