Intestinal Phospholipid Remodeling Is Required for Dietary-Lipid Uptake and Survival on a High-Fat Diet

被引：102

作者：

Wang, Bo ^{[1
,2
]}

Rong, Xin ^{[1
,2
]}

Duerr, Mark A.

Hermanson, Daniel J. ^{[5
]}

Hedde, Per Niklas ^{[6
,7
]}

Wong, Jinny S. ^{[8
]}

Vallim, Thomas Q. de Aguiar ^{[3
]}

Cravatt, Benjamin F. ^{[5
]}

Gratton, Enrico ^{[6
,7
]}

Ford, David A. ^{[4
]}

Tontonoz, Peter ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA

[4] St Louis Univ, Ctr Cardiovasc Res, Dept Biochem & Mol Biol, St Louis, MO 63104 USA

[5] Scripps Res Inst, Skaggs Inst Chem Biol, Dept Physiol Chem, La Jolla, CA 92037 USA

[6] Univ Calif Irvine, Dept Biomed Engn, Lab Fluorescence Dynam, Irvine, CA 92697 USA

[7] Univ Calif Irvine, Ctr Complex Biol Syst, Irvine, CA 92697 USA

[8] Gladstone Inst Cardiovasc Dis, Electron Microscopy Core, San Francisco, CA 94158 USA

来源：

CELL METABOLISM | 2016年 / 23卷 / 03期

关键词：

ACID TRANSPORT PROTEIN; BRUSH-BORDER MEMBRANE; FOOD-INTAKE; LYMPHATIC TRANSPORT; CHOLESTEROL UPTAKE; DEFICIENT RATS; LINOLEIC-ACID; CACO-2; CELLS; ABSORPTION; MICE;

D O I：

10.1016/j.cmet.2016.01.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Phospholipids are important determinants of membrane biophysical properties, but the impact of membrane acyl chain composition on dietary-lipid absorption is unknown. Here we demonstrate that the LXR-responsive phospholipid-remodeling enzyme Lpcat3 modulates intestinal fatty acid and cholesterol absorption and is required for survival on a high-fat diet. Mice lacking Lpcat3 in the intestine thrive on carbohydrate-based chow but lose body weight rapidly and become moribund on a triglyceride-rich diet. Lpcat3-dependent incorporation of polyunsaturated fatty acids into phospholipids is required for the efficient transport of dietary lipids into enterocytes. Furthermore, loss of Lpcat3 amplifies the production of gut hormones, including GLP-1 and oleoylethanolamide, in response to high-fat feeding, contributing to the paradoxical cessation of food intake in the setting of starvation. These results reveal that membrane phospholipid composition is a gating factor in passive lipid absorption and implicate LXR-Lpcat3 signaling in a gut-brain feedback loop that couples absorption to food intake.

引用

页码：492 / 504

页数：13

共 45 条

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