Expression of the Fatty Acid Receptors GPR84 and GPR120 and Cytodifferentiation of Epithelial Cells in the Gastric Mucosa of Mouse Pups in the Course of Dietary Transition.

Patricia Widmayer,Franziska A Hägele,Ulrich Boehm,Soumya Kusumakshi,Heinz Breer

doi:10.3389/fphys.2017.00601

Patricia Widmayer, Franziska A Hägele + Show 3 more

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https://doi.org/10.3389/fphys.2017.00601

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Abstract

During weaning, the ingested food of mouse pups changes from exclusively milk to solid food. In contrast to the protein- and carbohydrate-rich solid food, high fat milk is characterized primarily by fatty acids of medium chain length particularly important for the suckling pups. Therefore, it seems conceivable that the stomach mucosa may be specialized for detecting these important nutrients during the suckling phase. Here, we analyzed the expression of the G protein coupled receptors GPR84 and GPR120 (FFAR4), which are considered to be receptors for medium and long chain fatty acids (LCFAs), respectively. We found that the mRNA levels for GPR84 and GPR120 were high during the suckling period and progressively decreased in the course of weaning. Visualization of the receptor-expressing cells in 2-week-old mice revealed a high number of labeled cells, which reside in the apical as well as in the basal region of the gastric glands. At the base of the gastric glands, all GPR84-immunoreactive cells and some of the GPR120-positive cells also expressed chromogranin A (CgA), suggesting that they are enteroendocrine cells. We demonstrate that the majority of the CgA/GPR84 cells are X/A-like ghrelin cells. The high degree of overlap between ghrelin and GPR84 decreased post-weaning, whereas the overlap between ghrelin and GPR120 increased. At the apical region of the glands the fatty acid receptors were mainly expressed in unique cell types. These contain lipid-filled vacuole- and vesicle-like structures and may have absorptive functions. We detected decreased immunoreactivity for GPR84 and no lipid droplets in surface cells post-weaning. In conclusion, expression of GPR84 in ghrelin cells as well as in surface cells suggests an important role of medium chain fatty acids (MCFAs) in the developing gastric mucosa of suckling mice.

Highlights

During the postnatal development of mice, the structure and function of epithelial cells lining the gastrointestinal tract undergo changes in accordance with the physiological requirements at the different developmental stages (Kataoka et al, 1984)
The energy contained in mouse milk is mainly due to the high fat content, which is characterized by fatty acids of different carbon chain lengths ranging from 4 to 18 (Hahn and Koldovský, 1966; Görs et al, 2009), but primarily of medium chain fatty acids (MCFAs) with carbon chain lengths from 6 to 12 and long chain fatty acids (LCFAs) with a chain length of more than 12
In contrast to the protein- and carbohydrate-rich solid food after weaning, the suckling mouse pups entirely depend on high fat milk

Summary

Introduction

During the postnatal development of mice, the structure and function of epithelial cells lining the gastrointestinal tract undergo changes in accordance with the physiological requirements at the different developmental stages (Kataoka et al, 1984). The stomach mucosa remains immature during the entire suckling period and the small glands comprise of immature parietal and chief cells coinciding with low levels of acid and pepsin activity in the stomach (Keeley and Samuelson, 2010). During the late suckling period, at ∼3 weeks of age, the structure of the stomach mucosa changes in preparation for weaning— the turning point in diet type—, i.e., when milk is successively replaced by solid food of lower digestibility (Chen and Fisher, 1983). During the suckling-weaning transition, the diet changes from high fat milk to protein- and carbohydrate-rich food. We hypothesized that nutrient sensing in the stomach during the suckling phase strongly relies on receptors which recognize fatty acids and that fatty acid receptors may be less relevant later on when the mice ingest protein- and carbohydrate-rich food.

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