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

Article Article scientifique Article Dietary excess regulates absorption and surface of gut epithelium through intestinal PPARα eng 2021-12-02 2021-12-02 author Stojanovic Ozren 0000-0002-9418-3754 826171 author Altirriba Jordi author Rigo Dorothée 126299 author Spiljar Martina 860887 author Evrard Emilien Justin F 0000-0002-2565-1606 850509 author Roska Benedek 849798 author Fabbiano Salvatore 0000-0003-0768-6028 830542 author Zamboni Nicola author Maechler Pierre 0000-0002-2005-1433 76515 author Rohner-Jeanrenaud Françoise 26339 author Trajkovski Mirko 0000-0002-3152-9551 810468 7031 10.1038/s41467-021-27133-7 34857752 2041-1723 PMC8639731 https://www.nature.com/articles/s41467-021-27133-7 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. Dewey 612 Clayton foundation for biomedical research European Commission Microbiota-host interactions for integrative metabolic health reprogramming 815962 Healthybiota EU H2020 134 Département de physiologie cellulaire et métabolisme 21C false 724 Laboratory of metabolic diseases 934 402 Mitochondries et métabolisme énergétique 671 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74228 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE182348 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152056 Nature communications 12 1 43ae358b-7f97-491b-ad50-05b7b2a31c89 Article (Published version) Public Article-scientifique-from-unpaywall.pdf 2830994 application/pdf CC BY-4.0 99221e21-6111-4e0c-8d6b-b90962f03f3b Supplemental data Public 41467_2021_27133_MOESM5_ESM.xlsx 499311 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 31239465-8e5f-4c36-83fe-a047449efbb3 Appendix Public PMC8639731_SupplementaryFiles.zip 26318902 application/zip CC BY openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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Dietary excess regulates absorption and surface of gut epithelium through intestinal PPARα	Nature communications	2021	281	215

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