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蛋白质热量限制诱导了断奶大鼠后代的下丘脑-垂体-肾上腺(HPA)轴激活,并改变了其乳汁成分印记代谢。

Protein-caloric restriction induced HPA axis activation and altered the milk composition imprint metabolism of weaned rat offspring.

作者信息

Martins Isabela Peixoto, Vargas Rodrigo, Saavedra Lucas Paulo Jacinto, Rickli Sarah, Matiusso Camila Cristina Ianoni, Pavanello Audrei, Casagrande Lucas, Pastre Maria José, Oliveira Júlia Berno, de Almeida Ariadny Martins, de Souza Anna Carolina Huppes, de Oliveira Júlio Cezar, Malta Ananda, Mathias Paulo Cezar de Freitas

机构信息

Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringa, Maringa, PR, Brazil; Departament of Morphological Sciences, State University of Maringa, Maringa, PR, Brazil; Health Sciences Center, Unicesumar, Maringa, PR, Brazil.

Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringa, Maringa, PR, Brazil; Health Sciences Center, Unicesumar, Maringa, PR, Brazil.

出版信息

Nutrition. 2023 Apr;108:111945. doi: 10.1016/j.nut.2022.111945. Epub 2022 Dec 16.

DOI:10.1016/j.nut.2022.111945
PMID:36696704
Abstract

OBJECTIVES

Maternal protein-caloric restriction during lactation can malprogram offspring into having a lean phenotype associated with metabolic dysfunction in early life and adulthood. The aim of this study was to investigate the relationships between nutritional stress, maternal behavior and metabolism, milk composition, and offspring parameters. Additionally, we focused on the role of hypothalamus-pituitary-adrenal axis hyperactivation during lactation.

METHODS

Dams were fed a low-protein diet (4% protein) during the first 2 wk of lactation or a normal-protein diet (20% protein) during all lactation. Analyses of dams, milk, and offspring were conducted on postnatal days (PD) 7, 14, and 21.

RESULTS

Body weight and food intake decreased in dams, which was associated with reduced fat pad stores and increased corticosterone levels at PD 14. The stressed low-protein diet dams demonstrated alterations in behavior and offspring care. Despite nutritional deprivation, dams adapted their metabolism to provide adequate energy supply through milk; however, we demonstrated elevated corticosterone and total fat levels in milk at PD 14. Male offspring also showed increased corticosterone at PD 7, associated with a lean phenotype and alterations in white and brown adipose tissue morphology at PD 21.

CONCLUSION

Exposure to protein-caloric restriction diet of dams during lactation increased the glucocorticoid levels in dams, milk, and offspring, which is associated with alterations in maternal behavior and milk composition. Thus, glucocorticoids and milk composition may play an important role in metabolic programming induced by maternal undernutrition.

摘要

目的

哺乳期母体蛋白质-热量限制可使后代出现与生命早期和成年期代谢功能障碍相关的瘦型表型。本研究旨在探讨营养应激、母体行为与代谢、乳汁成分及后代参数之间的关系。此外,我们重点关注哺乳期下丘脑-垂体-肾上腺轴过度激活的作用。

方法

母鼠在哺乳期的前2周喂食低蛋白饮食(4%蛋白质),或在整个哺乳期喂食正常蛋白饮食(20%蛋白质)。在出生后第7、14和21天对母鼠、乳汁和后代进行分析。

结果

母鼠体重和食物摄入量下降,这与出生后第14天脂肪垫储存减少和皮质酮水平升高有关。应激的低蛋白饮食母鼠表现出行为和后代照料方面的改变。尽管营养缺乏,但母鼠通过乳汁调整其代谢以提供充足的能量供应;然而,我们发现出生后第14天乳汁中皮质酮和总脂肪水平升高。雄性后代在出生后第7天皮质酮也升高,这与出生后第21天的瘦型表型以及白色和棕色脂肪组织形态改变有关。

结论

哺乳期母鼠暴露于蛋白质-热量限制饮食会增加母鼠、乳汁和后代中的糖皮质激素水平,这与母体行为和乳汁成分的改变有关。因此,糖皮质激素和乳汁成分可能在母体营养不良诱导的代谢编程中起重要作用。

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