Hypothalamic endoplasmic reticulum stress and insulin resistance in offspring of mice dams fed high-fat diet during pregnancy and lactation

Author(s)

Melo, Arine M. ^[1] ; Benatti, Rafaela O. ^[1] ; Ignacio-Souza, Leticia M. ^[2] ; Okino, Caroline ^[1] ; Torsoni, Adriana S. ^{[1, 3]} ; Milanski, Marciane ^{[1, 3]} ; Velloso, Licio A. ^[4] ; Torsoni, Marcio Alberto ^{[1, 3]}

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Fac Sci Appl, Lab Metab Disorders, Sao Paulo - Brazil

^[2] Fed Univ Mato Grosso UFMT, Fac Nutr, Cuiaba, Mato Grosso - Brazil

^[3] Univ Estadual Campinas, UNICAMP, Fac Sci Appl, Ctr Studies Lipid Nutrigen, Sao Paulo - Brazil

^[4] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Lab Cell Signaling, Dept Internal Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: METABOLISM-CLINICAL AND EXPERIMENTAL; v. 63, n. 5, p. 682-692, MAY 2014.
• Web of Science Citations: 31

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. Materials/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-beta mRNA, NF kappa B 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-eIF2 alpha, 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 NF kappa B, p-JNK, p-PERK and p-eIF2 alpha. Conclusion. 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. (C) 2014 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 11/17656-0 - Modulation of hypothalamic AMPK and energy homeostasis by LPS: the role of toll like Receptor-4 (TLR-4)
• Grantee: Marcio Alberto Torsoni
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/50809-5 - Inflammation and immune response in obesity
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Projects - Thematic Grants