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

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• 作者：Arine M. Melo^a ; Rafaela O. Benatti^a ; Leticia M. Ignacio-Souza^b ; Caroline Okino^a ; Adriana S. Torsoni^a ; ^d ; Marciane Milanski^a ; ^d ; Licio A. Velloso^c ; Marcio Alberto Torsoni^a ; ^d ; ^{marcio.torsoni@fca.unicamp.br" class="auth_mail}
• 关键词：ACC ; acetyl-CoA carboxylase ; AGRP ; agouti-related polypeptide ; AKT ; protein kinase B ; AMPK ; 5' AMP-activated protein kinase ; ATF6 ; activating transcription factor 6 ; DIO ; diet-induced obesity ; eIF2伪 ; eukaryotic initiation factor 2伪 ; ER ; endoplasmic reticulum ; ERS ; endoplasmic reticulum stress ; FFA ; free fatty acids ; GAPDH ; glyceraldehyde 3-phosphate dehydrogenase ; GPR ; glucose-regulated protein ; GTT ; glucose tolerance test ; HFD ; high-fat diet ; HFD-O ; offspring from HFD dams ; ICV ; intracerebrov
• 刊名：Metabolism
• 出版年：May, 2014
• 年：2014
• 卷：63
• 期：5
• 页码：682-692
• 全文大小：1235 K

文摘

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-尾 mRNA, NF魏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伪, 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魏B, p-JNK, p-PERK and p-eIF2伪.

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.