title: Intestinal Phospholipid Remodeling Is Required for Dietary-Lipid Uptake and Survival on a High-Fat Diet.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Rong
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Cardiovascular Research, Saint Louis University, St. Louis, MO 63104, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Duerr
authors.affiliation: Department of Chemical Physiology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hermanson
authors.affiliation: Laboratory of Fluorescence Dynamics, Biomedical Engineering Department, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Per Niklas
authors.initials: PN
authors.lastname: Hedde
authors.affiliation: Electron Microscopy Core, Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
authors.forename: Jinny S
authors.initials: JS
authors.lastname: Wong
authors.affiliation: Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Thomas Q de Aguiar
authors.initials: TQ
authors.lastname: Vallim
authors.affiliation: Department of Chemical Physiology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
authors.affiliation: Laboratory of Fluorescence Dynamics, Biomedical Engineering Department, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Enrico
authors.initials: E
authors.lastname: Gratton
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Cardiovascular Research, Saint Louis University, St. Louis, MO 63104, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Ford
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: ptontonoz@mednet.ucla.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000378:metabolism; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D050356:Lipid Metabolism; D008297:Male; D008560:Membrane Fluidity; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000209:etiology; D010743:Phospholipids / Q000378:metabolism*; D015533:Transcriptional Activation; D014280:Triglycerides / Q000097:blood
chemical_list: D001053:Apolipoproteins; D004041:Dietary Fats; D010743:Phospholipids; D014280:Triglycerides; D052216:Glucagon-Like Peptide 1; D002784:Cholesterol; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C000600794:LPCAT3 protein, mouse
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