Dietary excess regulates absorption and surface of gut epithelium through intestinal PPARα.
Adiposity
/ genetics
Animals
Diet
/ methods
Eating
/ physiology
Fatty Liver
/ genetics
Gene Expression Regulation
Humans
Intestinal Absorption
/ physiology
Intestines
/ metabolism
Lipid Droplets
/ metabolism
Lipid Metabolism
/ genetics
Male
Mice
Mice, Transgenic
PPAR alpha
/ deficiency
Perilipin-2
/ genetics
Postprandial Period
Signal Transduction
Triglycerides
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 12 2021
02 12 2021
Historique:
received:
09
04
2021
accepted:
05
11
2021
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
5
1
2022
Statut:
epublish
Résumé
Intestinal surface changes in size and function, but what propels these alterations and what are their metabolic consequences is unknown. Here we report that the food amount is a positive determinant of the gut surface area contributing to an increased absorptive function, reversible by reducing daily food. While several upregulated intestinal energetic pathways are dispensable, the intestinal PPARα is instead necessary for the genetic and environment overeating-induced increase of the gut absorptive capacity. In presence of dietary lipids, intestinal PPARα knock-out or its pharmacological antagonism suppress intestinal crypt expansion and shorten villi in mice and in human intestinal biopsies, diminishing the postprandial triglyceride transport and nutrient uptake. Intestinal PPARα ablation limits systemic lipid absorption and restricts lipid droplet expansion and PLIN2 levels, critical for droplet formation. This improves the lipid metabolism, and reduces body adiposity and liver steatosis, suggesting an alternative target for treating obesity.
Identifiants
pubmed: 34857752
doi: 10.1038/s41467-021-27133-7
pii: 10.1038/s41467-021-27133-7
pmc: PMC8639731
doi:
Substances chimiques
PLIN2 protein, human
0
PPAR alpha
0
PPARA protein, human
0
Perilipin-2
0
Plin2 protein, mouse
0
Ppara protein, mouse
0
Triglycerides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7031Informations de copyright
© 2021. The Author(s).
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