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

M Dávalos-Salas; MK Montgomery; CM Reehorst; R Nightingale; I Ng; H Anderton; S Al-Obaidi; A Lesmana; CM Scott; P Ioannidis; H Kalra; S Keerthikumar; L Tögel; A Rigopoulos; SJ Gong; DS Williams; P Yoganantharaja; K Bell-Anderson; S Mathivanan; Y Gibert; S Hiebert; AM Scott; MJ Watt; JM Mariadason

Journal article

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

M Dávalos-Salas, MK Montgomery, CM Reehorst, R Nightingale, I Ng, H Anderton, S Al-Obaidi, A Lesmana, CM Scott, P Ioannidis, H Kalra, S Keerthikumar, L Tögel, A Rigopoulos, SJ Gong, DS Williams, P Yoganantharaja, K Bell-Anderson, S Mathivanan, Y Gibert Show all

Nature Communications | NATURE PUBLISHING GROUP | Published : 2019

DOI: 10.1038/s41467-019-13180-8

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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..

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University of Melbourne Researchers

Magda Montgomery Author

Shivakumar Keerthikumar Author

Andrew Scott Author

Matt Watt Author

Related Projects (1)

LIPID METABOLISM IN HEALTH AND DISEASE

Obesity is associated with type 2 diabetes, fatty liver disease, cardiovascular disease and cancer. These inter-related diseases reduce life..

Grants

Awarded by National Cancer Institute

Funding Acknowledgements

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.