Details

Autor(en) / Beteiligte

• Wang, Bo
• Rong, Xin
• Duerr, Mark A.
• Hermanson, Daniel J.
• Hedde, Per Niklas
• Wong, Jinny S.
• de Aguiar Vallim, Thomas Q.
• Cravatt, Benjamin F.
• Gratton, Enrico
• Ford, David A.
• Tontonoz, Peter

Titel

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

Ist Teil von

• Cell metabolism, 2016-03, Vol.23 (3), p.492-504

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• 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. [Display omitted] •Lpcat3 enzyme activity is critical for dietary-lipid absorption•Fatty acid uptake and chylomicron production require phospholipid remodeling•Lpcat3 is essential for the survival of mice fed high-fat, but not low-fat, diet•Loss of Lpcat3 amplifies the production of gut hormones and OEA on a high-fat diet Wang et al. show that intestinal Lpcat3, a phospholipid-remodeling enzyme, is required for dietary-lipid absorption. Lpcat3 deletion alters membrane fluidity, inhibits lipid transport into enterocytes, and amplifies the production of anorexic gut hormones in response to high-fat feeding, contributing to the paradoxical cessation of food intake despite starvation.