A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption

doi:10.1126/science.aao6575

	A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption
	Zhang, Ying-Yu 1,2; Fu, Zhen-Yan 3; Wei, Jian 2; Qi, Wei4 ; Baituola, Gulinaer 3; Luo, Jie 2; Meng, Ya-Jie 3; Guo, Shu-Yuan4,5 ; Yin, Huiyong4,5 ; Jiang, Shi-You 2; Li, Yun-Feng 2; Miao, Hong-Hua 1; Liu, Yong 2; Wang, Yan 2; Li, Bo-Liang 1; Ma, Yi-Tong 3; Song, Bao-Liang 2
	2018-06-08
发表期刊	SCIENCE (IF:44.7[JCR-2023],50.3[5-Year])
ISSN	0036-8075
卷号	360 期号:6393 页码:1087-1092
发表状态	已发表
DOI	10.1126/science.aao6575
摘要	A high concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. Although LDL-C levels vary among humans and are heritable, the genetic factors affecting LDL-C are not fully characterized. We identified a rare frameshift variant in the LIMA1 (also known as EPLIN or SREBP3) gene from a Chinese family of Kazakh ethnicity with inherited low LDL-C and reduced cholesterol absorption. In a mouse model, LIMA1 was mainly expressed in the small intestine and localized on the brush border membrane. LIMA1 bridged NPC1L1, an essential protein for cholesterol absorption, to a transportation complex containing myosin Vb and facilitated cholesterol uptake. Similar to the human phenotype, Lima1-deficient mice displayed reduced cholesterol absorption and were resistant to diet-induced hypercholesterolemia. Through our study of both mice and humans, we identify LIMA1 as a key protein regulating intestinal cholesterol absorption.
收录类别	SCI ; SCIE
语种	英语
资助项目	Natural Science Foundation of Hubei Province[2016CFA012]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000434635500038
出版者	AMER ASSOC ADVANCEMENT SCIENCE
WOS关键词	HEART-DISEASE ; NPC1L1 ; PROTEIN ; HYPERCHOLESTEROLEMIA ; EZETIMIBE ; RECEPTOR ; INTERNALIZATION ; COMPARTMENT ; MUTATIONS ; MEMBRANE
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/23080
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_尹慧勇组生命科学与技术学院_PI研究组_戚炜组生命科学与技术学院_博士生
通讯作者	Ma, Yi-Tong; Song, Bao-Liang
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China 2.Wuhan Univ, Inst Adv Studies, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Hubei, Peoples R China 3.Xinjiang Med Univ, State Key Lab Pathogenesis Prevent & Treatment Hi, Heart Ctr, Affiliated Hosp 1, Urumqi 830054, Xinjiang, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 5.Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Ying-Yu,Fu, Zhen-Yan,Wei, Jian,et al. A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption[J]. SCIENCE,2018,360(6393):1087-1092.
APA	Zhang, Ying-Yu.,Fu, Zhen-Yan.,Wei, Jian.,Qi, Wei.,Baituola, Gulinaer.,...&Song, Bao-Liang.(2018).A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption.SCIENCE,360(6393),1087-1092.
MLA	Zhang, Ying-Yu,et al."A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption".SCIENCE 360.6393(2018):1087-1092.