Intestinal Phospholipid Remodeling Is Required for Dietary-Lipid Uptake and Survival on a High-Fat Diet.
Intestinal Phospholipid Remodeling Is Required for Dietary-Lipid Uptake and Survival on a High-Fat Diet.
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DOI：
10.1016/j.cmet.2016.01.001
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发表时间：
2016-03-08
期刊：
影响因子：
29
通讯作者：
Tontonoz P
中科院分区：
文献类型：
--
作者：
Wang B;Rong X;Duerr MA;Hermanson DJ;Hedde PN;Wong JS;Vallim TQ;Cravatt BF;Gratton E;Ford DA;Tontonoz P
磷脂是膜生物物理性质的重要决定因素，但膜酰基链组成对膳食脂质吸收的影响尚不清楚。在这里，我们证明了LXR反应性磷脂重塑酶Lpcat 3调节肠道脂肪酸和胆固醇的吸收，是高脂饮食生存所必需的。肠道中缺乏Lpcat 3的小鼠在碳水化合物食物中茁壮成长，但体重迅速减轻，并在富含维生素D的饮食中变得奄奄一息。Lpcat 3依赖性的多不饱和脂肪酸与磷脂的结合是膳食脂质有效转运到肠上皮细胞中所必需的。此外，Lpcat 3的缺失放大了响应于高脂肪喂养的肠道激素（包括GLP-1和油酰乙醇胺）的产生，导致在饥饿环境中食物摄入的矛盾停止。这些结果表明，膜磷脂组合物是被动脂质吸收的门控因子，并涉及肠-脑反馈回路中的LXR-Lpcat 3信号传导，该反馈回路将吸收与食物摄入耦合。
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.