Journal article

Deletion of intestinal Hdac3 remodels the lipidome of enterocytes and protects mice from diet-induced obesity

Mercedes Davalos-Salas, Magdalene K Montgomery, Camilla M Reehorst, Rebecca Nightingale, Irvin Ng, Holly Anderton, Sheren Al-Obaidi, Analia Lesmana, Cameron M Scott, Paul Ioannidis, Hina Kalra, Shivakumar Keerthikumar, Lars Togel, Angela Rigopoulos, Sylvia J Gong, David S Williams, Prusoth Yoganantharaja, Kim Bell-Anderson, Suresh Mathivanan, Yann Gibert Show all

Nature Communications | NATURE PUBLISHING GROUP | Published : 2019

Abstract

Histone deacetylase 3 (Hdac3) regulates the expression of lipid metabolism genes in multiple tissues, however its role in regulating lipid metabolism in the intestinal epithelium is unknown. Here we demonstrate that intestine-specific deletion of Hdac3 (Hdac3IKO) protects mice from diet induced obesity. Intestinal epithelial cells (IECs) from Hdac3IKO mice display co-ordinate induction of genes and proteins involved in mitochondrial and peroxisomal β-oxidation, have an increased rate of fatty acid oxidation, and undergo marked remodelling of their lipidome, particularly a reduction in long chain triglycerides. Many HDAC3-regulated fatty oxidation genes are transcriptional targets of the PPAR..

View full abstract