作者
Mercedes Dávalos-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 Tögel, Angela Rigopoulos, Sylvia J Gong, David S Williams, Prusoth Yoganantharaja, Kim Bell-Anderson, Suresh Mathivanan, Yann Gibert, Scott Hiebert, Andrew M Scott, Matthew J Watt, John M Mariadason
发表日期
2019/11/22
期刊
Nature communications
卷号
10
期号
1
页码范围
5291
出版商
Nature Publishing Group UK
简介
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 …
学术搜索中的文章
M Dávalos-Salas, MK Montgomery, CM Reehorst… - Nature communications, 2019