title: Hypothalamic endoplasmic reticulum stress and insulin resistance in offspring of mice dams fed high-fat diet during pregnancy and lactation.
abstract: OBJECTIVE
  The goal of this study was to determine the presence early of markers of endoplasmic reticulum stress (ERS) and insulin resistance in the offspring from dams fed HFD (HFD-O) or standard chow diet (SC-O) during pregnancy and lactation.
  
  
  METHODS
  To address this question, we evaluated the hypothalamic and hepatic tissues in recently weaned mice (d28) and the hypothalamus of newborn mice (d0) from dams fed HFD or SC during pregnancy and lactation.
  
  
  RESULTS
  Body weight, adipose tissue mass, and food intake were more accentuated in HFD-O mice than in SC-O mice. In addition, intolerance to glucose and insulin was higher in HFD-O mice than in SC-O mice. Compared with SC-O mice, levels of hypothalamic IL1-β mRNA, NFκB protein, and p-JNK were increased in HFD-O mice. Furthermore, compared with SC-O mice, hypothalamic AKT phosphorylation after insulin challenge was reduced, while markers of ERS (p-PERK, p-eIF2α, XBP1s, GRP78, and GRP94) and p-AMPK were increased in the hypothalamic tissue of HFD-O at d28 but not at d0. These damages to hypothalamic signaling were accompanied by increased triglyceride deposits, activation of NFκB, p-JNK, p-PERK and p-eIF2α.
  
  
  CONCLUSIONS
  These point out lactation period as maternal trigger for metabolic changes in the offspring. These changes may occur early and quietly contribute to obesity and associated pathologies in adulthood. Although in rodents the establishment of ARC neuronal projections occurs during the lactation period, in humans it occurs during the third trimester. Gestational diabetes and obesity in this period may contribute to impairment of energy homeostasis.
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil.
authors.forename: Arine M
authors.initials: AM
authors.lastname: Melo
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil.
authors.forename: Rafaela O
authors.initials: RO
authors.lastname: Benatti
authors.affiliation: Faculty of Nutrition, Federal University of Mato Grosso-UFMT, Cuiabá, Mato Grosso, Brasil.
authors.forename: Leticia M
authors.initials: LM
authors.lastname: Ignacio-Souza
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Okino
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil; Center for Studies of lipid in Nutrigenomic, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil.
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Torsoni
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil; Center for Studies of lipid in Nutrigenomic, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil.
authors.forename: Marciane
authors.initials: M
authors.lastname: Milanski
authors.affiliation: Laboratoty of Cell Signaling, Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas-UNICAMP, Campinas, São Paulo, Brasil.
authors.forename: Licio A
authors.initials: LA
authors.lastname: Velloso
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil; Center for Studies of lipid in Nutrigenomic, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil. Electronic address: marcio.torsoni@fca.unicamp.br.
authors.forename: Marcio Alberto
authors.initials: MA
authors.lastname: Torsoni
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D007333:Insulin Resistance; D007774:Lactation / Q000187:drug effects / Q000502:physiology; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000187:drug effects; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse
keywords: Central nervous system; Inflammatory pathway; Maternal obesity; Metabolic imprinting