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Hypothalamic endoplasmic reticulum stress and insulin resistance in offspring of mice dams fed high-fat diet during pregnancy and lactation.
Metabolism. 2014 May; 63(5):682-92.M

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-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.

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.

Authors+Show Affiliations

Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil.Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil.Faculty of Nutrition, Federal University of Mato Grosso-UFMT, Cuiabá, Mato Grosso, Brasil.Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo, Brasil.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.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.Laboratoty of Cell Signaling, Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas-UNICAMP, Campinas, São Paulo, Brasil.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24636055

Citation

Melo, Arine M., et al. "Hypothalamic Endoplasmic Reticulum Stress and Insulin Resistance in Offspring of Mice Dams Fed High-fat Diet During Pregnancy and Lactation." Metabolism: Clinical and Experimental, vol. 63, no. 5, 2014, pp. 682-92.
Melo AM, Benatti RO, Ignacio-Souza LM, et al. Hypothalamic endoplasmic reticulum stress and insulin resistance in offspring of mice dams fed high-fat diet during pregnancy and lactation. Metabolism. 2014;63(5):682-92.
Melo, A. M., Benatti, R. O., Ignacio-Souza, L. M., Okino, C., Torsoni, A. S., Milanski, M., Velloso, L. A., & Torsoni, M. A. (2014). Hypothalamic endoplasmic reticulum stress and insulin resistance in offspring of mice dams fed high-fat diet during pregnancy and lactation. Metabolism: Clinical and Experimental, 63(5), 682-92. https://doi.org/10.1016/j.metabol.2014.02.002
Melo AM, et al. Hypothalamic Endoplasmic Reticulum Stress and Insulin Resistance in Offspring of Mice Dams Fed High-fat Diet During Pregnancy and Lactation. Metabolism. 2014;63(5):682-92. PubMed PMID: 24636055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypothalamic endoplasmic reticulum stress and insulin resistance in offspring of mice dams fed high-fat diet during pregnancy and lactation. AU - Melo,Arine M, AU - Benatti,Rafaela O, AU - Ignacio-Souza,Leticia M, AU - Okino,Caroline, AU - Torsoni,Adriana S, AU - Milanski,Marciane, AU - Velloso,Licio A, AU - Torsoni,Marcio Alberto, Y1 - 2014/02/10/ PY - 2013/09/18/received PY - 2014/02/04/revised PY - 2014/02/04/accepted PY - 2014/3/19/entrez PY - 2014/3/19/pubmed PY - 2014/6/5/medline KW - Central nervous system KW - Inflammatory pathway KW - Maternal obesity KW - Metabolic imprinting SP - 682 EP - 92 JF - Metabolism: clinical and experimental JO - Metabolism VL - 63 IS - 5 N2 - 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-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. 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. SN - 1532-8600 UR - https://www.unboundmedicine.com/medline/citation/24636055/Hypothalamic_endoplasmic_reticulum_stress_and_insulin_resistance_in_offspring_of_mice_dams_fed_high_fat_diet_during_pregnancy_and_lactation_ DB - PRIME DP - Unbound Medicine ER -