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
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
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Awarded by NHMRC
Awarded by NATIONAL CANCER INSTITUTE
This project was supported by NHMRC project grant (GNT1107836), NHMRC Senior Research Fellowships to J.M.M. (GNT1046092) and M.J.W. (GNT1077703), and the Operational Infrastructure Support Program, Victorian Government, Australia.