title: Loss of the PlagL2 transcription factor affects lacteal uptake of chylomicrons.
abstract: Enterocytes assemble dietary lipids into chylomicron particles that are taken up by intestinal lacteal vessels and peripheral tissues. Although chylomicrons are known to assemble in part within membrane secretory pathways, the modifications required for efficient vascular uptake are unknown. Here we report that the transcription factor pleomorphic adenoma gene-like 2 (PlagL2) is essential for this aspect of dietary lipid metabolism. PlagL2(-/-) mice die from postnatal wasting owing to failure of fat absorption. Lipids modified in the absence of PlagL2 exit from enterocytes but fail to enter interstitial lacteal vessels. Dysregulation of enterocyte genes closely linked to intracellular membrane transport identified candidate regulators of critical steps in chylomicron assembly. PlagL2 thus regulates important aspects of dietary lipid absorption, and the PlagL2(-/-) animal model has implications for the amelioration of obesity and the metabolic syndrome.
authors.affiliation: Department of Human Genetics, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Frederik
authors.initials: F
authors.lastname: Van Dyck
authors.forename: Caroline V
authors.initials: CV
authors.lastname: Braem
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.forename: Jeroen
authors.initials: J
authors.lastname: Declercq
authors.forename: Rob
authors.initials: R
authors.lastname: Deckers
authors.forename: Byeong-Moo
authors.initials: BM
authors.lastname: Kim
authors.forename: Susumu
authors.initials: S
authors.lastname: Ito
authors.forename: Michele K
authors.initials: MK
authors.lastname: Wu
authors.forename: David E
authors.initials: DE
authors.lastname: Cohen
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Rita
authors.initials: R
authors.lastname: Derua
authors.forename: Etienne
authors.initials: E
authors.lastname: Waelkens
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiette
authors.forename: Anton
authors.initials: A
authors.lastname: Roebroek
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Wim J M
authors.initials: WJ
authors.lastname: Van de Ven
authors.forename: Ramesh A
authors.initials: RA
authors.lastname: Shivdasani
mesh_terms: D000818:Animals; D001692:Biological Transport; D015152:Blotting, Northern; D002914:Chylomicrons / Q000378:metabolism* / Q000493:pharmacokinetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004041:Dietary Fats / Q000378:metabolism / Q000493:pharmacokinetics; D020895:Enterocytes / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D002914:Chylomicrons; D004268:DNA-Binding Proteins; D004041:Dietary Fats; C485426:Plagl2 protein, mouse; D016601:RNA-Binding Proteins; D014157:Transcription Factors