| First Author | Dávalos-Salas M | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 5291 |
| PubMed ID | 31757939 | Mgi Jnum | J:283938 |
| Mgi Id | MGI:6387959 | Doi | 10.1038/s41467-019-13180-8 |
| Citation | Davalos-Salas M, et al. (2019) Deletion of intestinal Hdac3 remodels the lipidome of enterocytes and protects mice from diet-induced obesity. Nat Commun 10(1):5291 |
| abstractText | 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 (Hdac3(IKO)) protects mice from diet induced obesity. Intestinal epithelial cells (IECs) from Hdac3(IKO) mice display co-ordinate induction of genes and proteins involved in mitochondrial and peroxisomal beta-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. |
