title: Maternal obesity alters endoplasmic reticulum homeostasis in offspring pancreas.
abstract: The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is increasing in parallel with obesity rates. Stress-related alterations in endoplasmic reticulum (ER), such as the unfolded protein response (UPR), are associated with obesity. The aim of this study was to investigate ER imbalance in the pancreas of a mice model of adult and perinatal diet-induced obesity. Twenty female C57BL/6J mice were assigned to control (Con) or obesogenic (Ob) diets prior to and during pregnancy and lactation. Their offspring were weaned onto Con or Ob diets up to 6 months post-partum. Then, after sacrifice, plasma biochemical analyses, gene expression, and protein concentrations were measured in pancreata. Offspring of Ob-fed mice had significantly increased body weight (p < 0.001) and plasma leptin (p < 0.001) and decreased insulin (p < 0.01) levels. Maternal obesogenic diet decreased the total and phosphorylated Eif2α and increased spliced X-box binding protein 1 (XBP1). Pancreatic gene expression of downstream regulators of UPR (EDEM, homocysteine-responsive endoplasmic reticulum-resident (HERP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP)) and autophagy-related proteins (LC3BI/LC3BII) were differently disrupted by obesogenic feeding in both mothers and offspring (from p < 0.1 to p < 0.001). Maternal obesity and Ob feeding in their offspring alter UPR in NAFPD, with involvement of proapoptotic and autophagy-related markers. Upstream and downstream regulators of PERK, IRE1α, and ATF6 pathways were affected differently following the obesogenic insults.
authors.affiliation: Institute for Liver and Digestive Health, University College London, London, UK.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Soeda
authors.affiliation: Institute for Liver and Digestive Health, University College London, London, UK.
authors.forename: Angelina
authors.initials: A
authors.lastname: Mouralidarane
authors.affiliation: Institute for Liver and Digestive Health, University College London, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Cordero
authors.affiliation: Institute for Liver and Digestive Health, University College London, London, UK.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute for Liver and Digestive Health, University College London, London, UK.
authors.forename: Vi
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: Institute for Liver and Digestive Health, University College London, London, UK.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Carter
authors.affiliation: Institute for Liver and Digestive Health, University College London, London, UK.
authors.forename: Sabrina R
authors.initials: SR
authors.lastname: Kapur
authors.affiliation: Division of Women's Health, King's College London, London, UK.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Pombo
authors.affiliation: Division of Women's Health, King's College London, London, UK.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.affiliation: Division of Women's Health, King's College London, London, UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Taylor
authors.affiliation: Institute for Liver and Digestive Health, University College London, London, UK. m.vinciguerra@ucl.ac.uk.|International Clinical Research Center (ICRC), Center for Translational Medicine (CTM), St. Anne's University Hospital, Brno, Czech Republic. m.vinciguerra@ucl.ac.uk.|Centro Studi Fegato (CSF)-Liver Research Center, Fondazione Italiana Fegato, Trieste, Italy. m.vinciguerra@ucl.ac.uk.
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
authors.affiliation: Institute for Liver and Digestive Health, University College London, London, UK. j.oben@ucl.ac.uk.|Department of Gastroenterology and Hepatology, Guy's and St Thomas' Hospital, NHS Foundation Trust, London, UK. j.oben@ucl.ac.uk.
authors.forename: Jude A
authors.initials: JA
authors.lastname: Oben
mesh_terms: D000818:Animals; D001343:Autophagy; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D019422:Dietary Sucrose / Q000009:adverse effects; D059865:Endoplasmic Reticulum Stress; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007328:Insulin / Q000097:blood; D007774:Lactation; D020738:Leptin / Q000097:blood; D039382:Maternal Nutritional Physiological Phenomena; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D010179:Pancreas / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D010195:Pancreatitis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000503:physiopathology*; D056811:Unfolded Protein Response; D014886:Weaning
chemical_list: D015415:Biomarkers; D019422:Dietary Sucrose; D007328:Insulin; D020738:Leptin
keywords: Autophagy; ER stress; Fatty pancreas; Obesity; Perinatal programming; UPR