title: Hepatic rhythmicity of endoplasmic reticulum stress is disrupted in perinatal and adult mice models of high-fat diet-induced obesity.
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 (IREα, 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.
authors.affiliation: a Institute for Liver and Digestive Health, University College London , London , UK.
authors.forename: Junpei
authors.initials: J
authors.lastname: Soeda
authors.affiliation: a Institute for Liver and Digestive Health, University College London , London , UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Cordero
authors.affiliation: a Institute for Liver and Digestive Health, University College London , London , UK.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Li
authors.affiliation: a Institute for Liver and Digestive Health, University College London , London , UK.
authors.forename: Angelina
authors.initials: A
authors.lastname: Mouralidarane
authors.affiliation: a Institute for Liver and Digestive Health, University College London , London , UK.
authors.forename: Esra
authors.initials: E
authors.lastname: Asilmaz
authors.affiliation: a Institute for Liver and Digestive Health, University College London , London , UK.
authors.forename: Shuvra
authors.initials: S
authors.lastname: Ray
authors.affiliation: a Institute for Liver and Digestive Health, University College London , London , UK.
authors.forename: Vi
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: a Institute for Liver and Digestive Health, University College London , London , UK.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Carter
authors.affiliation: b Department of Pathology , University College London , London , UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Novelli
authors.affiliation: a Institute for Liver and Digestive Health, 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.
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
authors.affiliation: e Division of Women's Health , King's College London , London , UK.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.affiliation: e Division of Women's Health , King's College London , London , UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Taylor
authors.affiliation: a Institute for Liver and Digestive Health, University College London , London , UK.|f Department of Gastroenterology and Hepatology , Guy's and St Thomas' Hospital, NHS Foundation Trust , London , UK.
authors.forename: Jude A
authors.initials: JA
authors.lastname: Oben
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006706:Homeostasis; D008099:Liver / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013312:Stress, Physiological / Q000187:drug effects*
keywords: ER stress; NAFLD; Obesity; circadian rhythm; developmental programming