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Title: | Deletion of intestinal Hdac3 remodels the lipidome of enterocytes and protects mice from diet-induced obesity. | Austin 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 | Date: | 2019 | Publication information: | 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: | https://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 |
Journal: | Nature Communications | PubMed URL: | 31757939 | Type: | Journal Article |
Appears in Collections: | Journal articles |
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