气候变化领域集成服务门户(CCPortal): Active p38α causes macrovesicular fatty liver in mice

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DOI	10.1073/pnas.2018069118
	Active p38α causes macrovesicular fatty liver in mice
	Darlyuk-Saadon I.; Bai C.; Heng C.K.M.; Gilad N.; Yu W.-P.; Lim P.Y.; Cazenave-Gassiot A.; Zhang Y.; Fred Wong W.S.; Engelberg D.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	One third of the western population suffers from nonalcoholic fatty liver disease (NAFLD), which may ultimately develop into hepatocellular carcinoma (HCC). The molecular event(s) that triggers the disease are not clear. Current understanding, known as the multiple hits model, suggests that NAFLD is a result of diverse events at several tissues (e.g., liver, adipose tissues, and intestine) combined with changes in metabolism and microbiome. In contrast to this prevailing concept, we report that fatty liver could be triggered by a single mutated protein expressed only in the liver. We established a transgenic system that allows temporally controlled activation of the MAP kinase p38α in a tissue-specific manner by induced expression of intrinsically active p38α allele. Here we checked the effect of exclusive activation in the liver. Unexpectedly, induction of p38α alone was sufficient to cause macrovesicular fatty liver. Animals did not become overweight, showing that fatty liver can be imposed solely by a genetic modification in liver per se and can be separated from obesity. Active p38α- induced fatty liver is associated with up-regulation of MUC13, CIDEA, PPARγ, ATF3, and c-jun mRNAs, which are up-regulated in human HCC. Shutting off expression of the p38α mutant resulted in reversal of symptoms. The findings suggest that p38α plays a direct causative role in fatty liver diseases and perhaps in other chronic inflammatory diseases. As p38α activity was induced by point mutations, it could be considered a proto-inflammatory gene (proto-inflammagene). © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Active variants; Fatty liver; Lipidosis; p38; Transgenic mice
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179948
作者单位	Singapore-HUJ Alliance for Research and Enterprise Molecular Mechanisms of Inflammatory Diseases Program, National University of Singapore, Singapore, 138602, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117456, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore, 117600, Singapore; Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel; Animal Gene Editing Laboratory (AGEL), Biological Resource Centre, Agency for Science, Technology and Research (ASTAR), Proteos, 138673, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Proteos, 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117456, Singapore; Immunology Programme, Life Science Institute, National Univer...
推荐引用方式 GB/T 7714	Darlyuk-Saadon I.,Bai C.,Heng C.K.M.,et al. Active p38α causes macrovesicular fatty liver in mice[J],2021,118(14).
APA	Darlyuk-Saadon I..,Bai C..,Heng C.K.M..,Gilad N..,Yu W.-P..,...&Engelberg D..(2021).Active p38α causes macrovesicular fatty liver in mice.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Darlyuk-Saadon I.,et al."Active p38α causes macrovesicular fatty liver in mice".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).