Dietary excess regulates absorption and surface of gut epithelium through intestinal PPARα

Ozren Stojanović, Jordi Altirriba, Dorothée Rigo, Martina Spiljar, Emilien Evrard, Benedek Roska, Salvatore Fabbiano, Nicola Zamboni, Pierre Maechler, Françoise Rohner-Jeanrenaud and Mirko Trajkovski ()
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Ozren Stojanović: University of Geneva
Jordi Altirriba: University of Geneva
Dorothée Rigo: University of Geneva
Martina Spiljar: University of Geneva
Emilien Evrard: University of Geneva
Benedek Roska: University of Geneva
Salvatore Fabbiano: University of Geneva
Nicola Zamboni: Institute for Molecular Systems Biology, Swiss Federal Institute of Technology (ETH) Zurich
Pierre Maechler: University of Geneva
Françoise Rohner-Jeanrenaud: University of Geneva
Mirko Trajkovski: University of Geneva

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27133-7

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DOI: 10.1038/s41467-021-27133-7

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