气候变化领域集成服务门户(CCPortal): Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis

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DOI	10.1073/pnas.2006478118
	Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis
	Price N.L.; Zhang X.; Fernández-Tussy P.; Singh A.K.; Burnap S.A.; Rotllan N.; Goedeke L.; Sun J.; Canfrán-Duque A.; Aryal B.; Mayr M.; Suárez Y.; Fernández-Hernando C.
发表日期	2021
ISSN	00278424
卷号	118 期号:5
英文摘要	miR-33 is an intronic microRNA within the gene encoding the SREBP2 transcription factor. Like its host gene, miR-33 has been shown to be an important regulator of lipid metabolism. Inhibition of miR-33 has been shown to promote cholesterol efflux in macrophages by targeting the cholesterol transporter ABCA1, thus reducing atherosclerotic plaque burden. Inhibition of miR-33 has also been shown to improve high-density lipoprotein (HDL) biogenesis in the liver and increase circulating HDL-C levels in both rodents and nonhuman primates. However, evaluating the extent to which these changes in HDL metabolism contribute to atherogenesis has been hindered by the obesity and metabolic dysfunction observed in whole-body miR-33–knockout mice. To determine the impact of hepatic miR-33 deficiency on obesity, metabolic function, and atherosclerosis, we have generated a conditional knockout mouse model that lacks miR-33 only in the liver. Characterization of this model demonstrates that loss of miR-33 in the liver does not lead to increased body weight or adiposity. Hepatic miR-33 deficiency actually improves regulation of glucose homeostasis and impedes the development of fibrosis and inflammation. We further demonstrate that hepatic miR-33 deficiency increases circulating HDL-C levels and reverse cholesterol transport capacity in mice fed a chow diet, but these changes are not sufficient to reduce atherosclerotic plaque size under hyperlipidemic conditions. By elucidating the role of miR-33 in the liver and the impact of hepatic miR-33 deficiency on obesity and atherosclerosis, this work will help inform ongoing efforts to develop novel targeted therapies against cardiometabolic diseases. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Atherosclerosis; Fibrosis; Metabolism; MiRNA; Obesity
语种	英语
scopus关键词	alpha smooth muscle actin; high density lipoprotein cholesterol; microRNA; miR 33; stress activated protein kinase; unclassified drug; animal cell; animal experiment; animal model; animal tissue; Article; atherogenesis; atherosclerosis; body weight; carbon tetrachloride-induced liver fibrosis; cholesterol transport; controlled study; diet-induced obesity; female; glucose homeostasis; hepatic stellate cell; hepatitis; hypercholesterolemia; hyperlipidemia; insulin resistance; liver function; male; metabolic balance; metabolic regulation; mouse; nonhuman; priority journal
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/180813
作者单位	Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, United States; Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, United States; King’s College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, King’s College London, London, WC2R 2LS, United Kingdom; Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, United States
推荐引用方式 GB/T 7714	Price N.L.,Zhang X.,Fernández-Tussy P.,et al. Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis[J],2021,118(5).
APA	Price N.L..,Zhang X..,Fernández-Tussy P..,Singh A.K..,Burnap S.A..,...&Fernández-Hernando C..(2021).Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America,118(5).
MLA	Price N.L.,et al."Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis".Proceedings of the National Academy of Sciences of the United States of America 118.5(2021).