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...

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Bibliographic Details
Published in:Cell metabolism 2007-11, Vol.6 (5), p.406-413
Main Authors: Van Dyck, Frederik, Braem, Caroline V., Chen, Zhao, Declercq, Jeroen, Deckers, Rob, Kim, Byeong-Moo, Ito, Susumu, Wu, Michele K., Cohen, David E., Dewerchin, Mieke, Derua, Rita, Waelkens, Etienne, Fiette, Laurence, Roebroek, Anton, Schuit, Frans, Van de Ven, Wim J.M., Shivdasani, Ramesh A.
Format: Article
Language:English
Subjects:
Animals
Biological Transport
Blotting, Northern
Chylomicrons - metabolism
Chylomicrons - pharmacokinetics
Dietary Fats - metabolism
Dietary Fats - pharmacokinetics
DNA
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Enterocytes - metabolism
HUMDISEASE
Immunohistochemistry
Intestine, Small - metabolism
Intestines - metabolism
Lipid Metabolism
Mice
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
RNA-Binding Proteins - genetics
RNA-Binding Proteins - physiology
Transcription Factors - genetics
Transcription Factors - physiology
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Summary: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.
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2007.09.010