Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/22167
Title: Deletion of intestinal Hdac3 remodels the lipidome of enterocytes and protects mice from diet-induced obesity.
Authors: Dávalos-Salas, Mercedes;Montgomery, Magdalene K;Reehorst, Camilla M;Nightingale, Rebecca;Ng, Irvin;Anderton, Holly;Al-Obaidi, Sheren;Lesmana, Analia;Scott, Cameron M;Ioannidis, Paul;Kalra, Hina;Keerthikumar, Shivakumar;Tögel, Lars;Rigopoulos, Angela;Gong, Sylvia J;Williams, David S;Yoganantharaja, Prusoth;Bell-Anderson, Kim;Mathivanan, Suresh;Gibert, Yann;Hiebert, Scott;Scott, Andrew M;Watt, Matthew J;Mariadason, John M
Affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
La Trobe University School of Cancer Medicine, Melbourne, Victoria, Australia
Department of Physiology, Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
La Trobe Institute for Molecular Sciences, La Trobe University, Melbourne, Victoria, Australia
Department of Pathology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine, Deakin University, Geelong, Victoria, Australia
Faculty of Science, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
Vanderbilt University, Nashville, TN, USA
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
Department of Physiology, Faculty of Medicine Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
Issue Date: 22-Nov-2019
EDate: 2019
Citation: Nature communications 2019; 10(1): 5291
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 family of nuclear receptors, Hdac3 deletion enhances their induction by PPAR-agonists, and pharmacological HDAC3 inhibition induces their expression in enterocytes. These findings establish a central role for HDAC3 in co-ordinating PPAR-regulated lipid oxidation in the intestinal epithelium, and identify intestinal HDAC3 as a potential therapeutic target for preventing obesity and related diseases.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22167
DOI: 10.1038/s41467-019-13180-8
ORCID: 0000-0003-0692-5904
0000-0002-8039-3582
0000-0002-1357-4666
0000-0003-3913-9686
0000-0002-1003-7478
0000-0003-0612-6440
0000-0002-7761-3441
0000-0002-7290-5795
0000-0001-9123-7684
0000-0002-6656-295X
PubMed URL: 31757939
Type: Journal Article
Appears in Collections:Journal articles

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