Intestinal phospholipid remodeling is required for dietary-lipid uptake and survival on a high-fat diet

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)492-504
Number of pages13
JournalCell Metabolism
Issue number3
StatePublished - Mar 8 2016
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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