Loss of the PlagL2 transcription factor affects lacteal uptake of chylomicrons.
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.
Van Dyck
Frederik
F
Department of Human Genetics, University of Leuven, B-3000 Leuven, Belgium.
Braem
Caroline V
CV
Chen
Zhao
Z
Declercq
Jeroen
J
Deckers
Rob
R
Kim
Byeong-Moo
BM
Ito
Susumu
S
Wu
Michele K
MK
Cohen
David E
DE
Dewerchin
Mieke
M
Derua
Rita
R
Waelkens
Etienne
E
Fiette
Laurence
L
Roebroek
Anton
A
Schuit
Frans
F
Van de Ven
Wim J M
WJ
Shivdasani
Ramesh A
RA
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*
D002914:Chylomicrons; D004268:DNA-Binding Proteins; D004041:Dietary Fats; C485426:Plagl2 protein, mouse; D016601:RNA-Binding Proteins; D014157:Transcription Factors