UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Impaired LXRα Phosphorylation Attenuates Progression of Fatty Liver Disease

Becares, N; Gage, MC; Voisin, M; Shrestha, E; Martin-Gutierrez, L; Liang, N; Louie, R; ... Pineda-Torra, I; + view all (2019) Impaired LXRα Phosphorylation Attenuates Progression of Fatty Liver Disease. Cell Reports , 26 (4) 984-995.e6. 10.1016/j.celrep.2018.12.094. Green open access

[thumbnail of Becares_1-s2.0-S2211124718320540-main.pdf]
Preview
Text
Becares_1-s2.0-S2211124718320540-main.pdf - Published version

Download (3MB) | Preview

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a very common indication for liver transplantation. How fat-rich diets promote progression from fatty liver to more damaging inflammatory and fibrotic stages is poorly understood. Here, we show that disrupting phosphorylation at Ser196 (S196A) in the liver X receptor alpha (LXRα, NR1H3) retards NAFLD progression in mice on a high-fat-high-cholesterol diet. Mechanistically, this is explained by key histone acetylation (H3K27) and transcriptional changes in pro-fibrotic and pro-inflammatory genes. Furthermore, S196A-LXRα expression reveals the regulation of novel diet-specific LXRα-responsive genes, including the induction of Ces1f, implicated in the breakdown of hepatic lipids. This involves induced H3K27 acetylation and altered LXR and TBLR1 cofactor occupancy at the Ces1f gene in S196A fatty livers. Overall, impaired Ser196-LXRα phosphorylation acts as a novel nutritional molecular sensor that profoundly alters the hepatic H3K27 acetylome and transcriptome during NAFLD progression placing LXRα phosphorylation as an alternative anti-inflammatory or anti-fibrotic therapeutic target.

Type: Article
Title: Impaired LXRα Phosphorylation Attenuates Progression of Fatty Liver Disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2018.12.094
Publisher version: https://doi.org/10.1016/j.celrep.2018.12.094
Language: English
Additional information: © 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: fibrosis, inflammation, lipid metabolism, liver, liver X receptor, non-alcoholic fatty liver disease, phosphorylation, transcription
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10067015
Downloads since deposit
65Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item