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. 2023 Aug 17;18(8):e0290043.
doi: 10.1371/journal.pone.0290043. eCollection 2023.

Gut-derived peptide hormone receptor expression in the developing mouse hypothalamus

Lídia Cantacorps  1   2 , Bethany M Coull  1 , Joanne Falck  1 , Katrin Ritter  1 , Rachel N Lippert  1   2   3
Affiliations

Gut-derived peptide hormone receptor expression in the developing mouse hypothalamus

Lídia Cantacorps et al. PLoS One. .

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: This comprehensive analysis underscores the need to understand the roles of maternal-derived circulating gut hormones and their direct effect on offspring brain development.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Physiological characteristics across development and insulin receptor expression postnatally.
A) Hypothalamic samples were collected at timepoints across development for analysis. B) Body weight and C) blood glucose levels of male and female offspring were analyzed. InsR protein expression in D) males and E) females across early postnatal development. Open circles (males) or squares (females) represent individual data points. Data is plotted as Mean ± SEM * = p<0.05, ** = p<0.01.
Fig 2
Fig 2. Cholecystokinin 2 receptor, glucagon-like peptide receptor and Gastric inhibitory polypeptide receptor expression in postnatal development.
Cckbr mRNA expression across postnatal days in A) males and D) female animals. CCK2R protein expression in G) males and J) females across early postnatal development. Glp1r mRNA expression across postnatal days in B) males and E) female animals. GLP1R protein expression in H) males and K) females across early postnatal development. Gipr mRNA expression across postnatal days in C) males and F) female animals. GIPR protein expression in I) males and L) females across early postnatal development. Open circles (males) or squares (females) represent individual data points. Representative blots are shown for each protein assessed. Data is plotted as Mean ± SEM * = p<0.05, ** = p<0.01, *** = p<0.001, **** = p<0.0001.
Fig 3
Fig 3. Protein expression correlations with glucose levels and body weight.
INSR (A), CCK2R (B), GLP1R (C) and GIPR (D) protein expression across development in both sexes correlated with glucose (mg/dL) levels. INSR (E), CCK2R (F), GLP1R (G) and GIPR (H) protein expression across development in both sexes correlated with body weight. Circles (males) or squares (females) represent individual data points, color-coded by age.
Fig 4
Fig 4. Spatial distribution of Insr, Cckbr and Glp1r mRNA expression in the developing hypothalamus.
In situ hybridization images from the Allen Developing Mouse Brain Atlas (http://developingmouse.brain-map.org/) corresponding to the Insr (A, developingmouse.brain-map.org/gene/show/16110), Cckbr (B, developingmouse.brain-map.org/gene/show/12211) and Glp1r (C, developingmouse.brain-map.org/gene/show/14428) across early postnatal period (P4, P14 and P28) are represented.
Fig 5
Fig 5. Protein expression correlation with circulating leptin levels.
INSR (A), CCK2R (B), GLP1R (C) and GIPR (D) protein expression across development in both sexes was correlated with circulating leptin levels (ng/mL).
See this image and copyright information in PMC

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