| Title: | Hepatic rhythmicity of endoplasmic reticulum stress is disrupted in perinatal and adult mice models of high-fat diet-induced obesity |
| Author(s): | Soeda J; Cordero P; Li J; Mouralidarane A; Asilmaz E; Ray S; Nguyen V; Carter R; Novelli M; Vinciguerra M; Poston L; Taylor PD; Oben JA; |
| Address: | "a Institute for Liver and Digestive Health, University College London , London , UK. b Department of Pathology , University College London , London , UK. c Fondazione Italiana Fegato , Area Science Park , Basovizza , Trieste , Italy. d Center for Translational Medicine (CTM), International Clinical Research Center (ICRC), St. Anne's University Hospital , Brno , Czech Republic. e Division of Women's Health , King's College London , London , UK. f Department of Gastroenterology and Hepatology , Guy's and St Thomas' Hospital, NHS Foundation Trust , London , UK" |
| DOI: | 10.1080/09637486.2016.1261086 |
| ISSN/ISBN: | 1465-3478 (Electronic) 0963-7486 (Print) 0963-7486 (Linking) |
| Abstract: | "We investigated the regulation of hepatic ER stress in healthy liver and adult or perinatally programmed diet-induced non-alcoholic fatty liver disease (NAFLD). Female mice were fed either obesogenic or control diet before mating, during pregnancy and lactation. Post-weaning, offspring from each maternal group were divided into either obesogenic or control diet. At six months, offspring were sacrificed at 4-h intervals over 24 h. Offspring fed obesogenic diets developed NAFLD phenotype, and the combination of maternal and offspring obesogenic diets exacerbated this phenotype. UPR signalling pathways (IREalpha, PERK, ATF6) and their downstream regulators showed different basal rhythmicity, which was modified in offspring exposed to obesogenic diet and maternal programming. The double obesogenic hit increased liver apoptosis measured by TUNEL staining, active caspase-3 and phospho-JNK and GRP78 promoter methylation levels. This study demonstrates that hepatic UPR is rhythmically activated. The combination of maternal obesity (MO) and obesogenic diets in offspring triggered altered UPR rhythmicity, DNA methylation and cellular apoptosis" |
| Keywords: | "Animal Feed/analysis Animals Diet, High-Fat/*adverse effects Endoplasmic Reticulum/*physiology Endoplasmic Reticulum Chaperone BiP Female Homeostasis Liver/*drug effects Mice Mice, Inbred C57BL Obesity/*chemically induced/metabolism Pregnancy Prenatal Exp;" |
| Notes: | "MedlineSoeda, Junpei Cordero, Paul Li, Jiawei Mouralidarane, Angelina Asilmaz, Esra Ray, Shuvra Nguyen, Vi Carter, Rebeca Novelli, Marco Vinciguerra, Manlio Poston, Lucilla Taylor, Paul D Oben, Jude A eng WT_/Wellcome Trust/United Kingdom BB/H008845/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom England 2016/12/03 Int J Food Sci Nutr. 2017 Jun; 68(4):455-466. doi: 10.1080/09637486.2016.1261086. Epub 2016 Nov 29" |
