Department of Neurocircuit Development and Function, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
PLoS One. 2023 Aug 17;18(8):e0290043. doi: 10.1371/journal.pone.0290043. eCollection 2023.
In adult organisms, a number of receptors have been identified which modulate metabolic processes related to peptides derived from the intestinal tract. These receptors play significant roles in glucose homeostasis, food intake and energy balance. Here we assess these classical metabolic receptors and their expression as well as their potential role in early development of hypothalamic neuronal circuits.
Chow-fed C57BL6/N female mice were mated and hypothalamic tissue was collected from offspring across postnatal development (postnatal day 7-21). Subsequent qPCR and Western Blot analyses were used to determine mRNA and protein changes in gut-derived peptide hormone receptors. Correlations to body weight, blood glucose and circulating leptin levels were analyzed.
We describe the gene expression and dynamic protein regulation of key gut-derived peptide hormone receptors in the early postnatal period of the mouse brain. Specifically, we show changes to Gastric inhibitory polypeptide receptor (GIPR), glucagon-like peptide 1 receptor (GLP1R), and cholecystokinin receptor 2 (CCK2R) in the developing hypothalamus. The changes to GIPR and InsR seem to be strongly negatively correlated with body weight.
This comprehensive analysis underscores the need to understand the roles of maternal-derived circulating gut hormones and their direct effect on offspring brain development.
在成年生物体内，已经鉴定出许多受体，这些受体调节与肠道来源的肽相关的代谢过程。这些受体在葡萄糖稳态、食物摄入和能量平衡中发挥重要作用。在这里，我们评估这些经典代谢受体及其表达，以及它们在下丘脑神经元回路早期发育中的潜在作用。
给予 Chow 喂养的 C57BL6/N 雌性小鼠交配，并在后代的整个出生后发育阶段（出生后第 7-21 天）收集下丘脑组织。随后进行 qPCR 和 Western Blot 分析，以确定肠道来源的肽激素受体的 mRNA 和蛋白变化。分析与体重、血糖和循环瘦素水平的相关性。
我们描述了在小鼠大脑的早期出生后时期关键肠道来源的肽激素受体的基因表达和动态蛋白调节。具体而言，我们显示了胃抑制肽受体（GIPR）、胰高血糖素样肽 1 受体（GLP1R）和胆囊收缩素受体 2（CCK2R）在发育中的下丘脑中的变化。GIPR 和 InsR 的变化似乎与体重呈强烈负相关。
这项全面的分析强调了需要了解母体来源的循环肠道激素的作用及其对后代大脑发育的直接影响。
