2. Academic Validation
  3. Dietary excess regulates absorption and surface of gut epithelium through intestinal PPARα

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

  • Nat Commun. 2021 Dec 2;12(1):7031. doi: 10.1038/s41467-021-27133-7.
Ozren Stojanović 1 2 3,  Jordi Altirriba 1,  Dorothée Rigo 1 2,  Martina Spiljar 1 2,  Emilien Evrard 1,  Benedek Roska 1,  Salvatore Fabbiano 1 2,  Nicola Zamboni 4,  Pierre Maechler 1 2,  Françoise Rohner-Jeanrenaud 1,  Mirko Trajkovski 5 6
Affiliations

Affiliations

  • 1 Department of Cell Physiology and Metabolism, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  • 2 Diabetes Centre, Faculty of Medicine, University of Geneva, 1211, Geneva, Switzerland.
  • 3 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
  • 4 Institute for Molecular Systems Biology, Swiss Federal Institute of Technology (ETH) Zurich, 8093, Zurich, Switzerland.
  • 5 Department of Cell Physiology and Metabolism, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, Geneva, Switzerland. mirko.trajkovski@unige.ch.
  • 6 Diabetes Centre, Faculty of Medicine, University of Geneva, 1211, Geneva, Switzerland. mirko.trajkovski@unige.ch.
PMID: 34857752 DOI: 10.1038/s41467-021-27133-7
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-114263
    99.07%, PPAR Antagonist