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

Ying-Yu Zhang; Zhen-Yan Fu; Jian Wei; Wei Qi; Gulinaer Baituola; Jie Luo; Ya-Jie Meng; Shu-Yuan Guo; Huiyong Yin; Shi-You Jiang; Yun-Feng Li; Hong-Hua Miao; Yong Liu; Yan Wang; Bo-Liang Li; Yi-Tong Ma; Bao-Liang Song

doi:10.1126/science.aao6575

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

Ying-Yu Zhang
, Zhen-Yan Fu
, Jian Wei
, Wei Qi
, Gulinaer Baituola
, Jie Luo
, Ya-Jie Meng
, Shu-Yuan Guo
, Huiyong Yin
, Shi-You Jiang
, Yun-Feng Li
, Hong-Hua Miao
, Yong Liu
, Yan Wang
, Bo-Liang Li
, Yi-Tong Ma^*
, Bao-Liang Song

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

118 Citations (Scopus)

Abstract

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. © 2018 American Association for the Advancement of Science. All rights reserved.

Original language	English
Pages (from-to)	1087-1092
Journal	Science
Volume	360
Issue number	6393
DOIs	https://doi.org/10.1126/science.aao6575
Publication status	Published - 8 Jun 2018
Externally published	Yes

Bibliographical note

Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

Funding

This work was supported by grants from the MOST of China (2016YFA0500100), NNSF of China (31690102, 31430044, 81260041, 31771568, 31701030, 91754102, U1403221, and 31600651), Xinjiang Key Research and Development Project (2016B03053), Science and Technology Support Project of Xinjiang (2017E0269), 111 Project of Ministry of Education of China (B16036), and the Natural Science Foundation of Hubei Province (2016CFA012).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Zhang, Y.-Y., Fu, Z.-Y., Wei, J., Qi, W., Baituola, G., Luo, J., Meng, Y.-J., Guo, S.-Y., Yin, H., Jiang, S.-Y., Li, Y.-F., Miao, H.-H., Liu, Y., Wang, Y., Li, B.-L., Ma, Y.-T., & Song, B.-L. (2018). A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption. Science, 360(6393), 1087-1092. https://doi.org/10.1126/science.aao6575

@article{535d8020c3564e6da16fa8756a052609,

title = "A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption",

abstract = "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. {\textcopyright} 2018 American Association for the Advancement of Science. All rights reserved.",

author = "Ying-Yu Zhang and Zhen-Yan Fu and Jian Wei and Wei Qi and Gulinaer Baituola and Jie Luo and Ya-Jie Meng and Shu-Yuan Guo and Huiyong Yin and Shi-You Jiang and Yun-Feng Li and Hong-Hua Miao and Yong Liu and Yan Wang and Bo-Liang Li and Yi-Tong Ma and Bao-Liang Song",

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T1 - A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption

AU - Zhang, Ying-Yu

AU - Fu, Zhen-Yan

AU - Wei, Jian

AU - Qi, Wei

AU - Baituola, Gulinaer

AU - Luo, Jie

AU - Meng, Ya-Jie

AU - Guo, Shu-Yuan

AU - Yin, Huiyong

AU - Jiang, Shi-You

AU - Li, Yun-Feng

AU - Miao, Hong-Hua

AU - Liu, Yong

AU - Wang, Yan

AU - Li, Bo-Liang

AU - Ma, Yi-Tong

AU - Song, Bao-Liang

N1 - Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

PY - 2018/6/8

Y1 - 2018/6/8

N2 - 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. © 2018 American Association for the Advancement of Science. All rights reserved.

AB - 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. © 2018 American Association for the Advancement of Science. All rights reserved.

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DO - 10.1126/science.aao6575

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EP - 1092

JO - Science

JF - Science

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

Abstract

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Funding

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