# Gastric and Small-Intestinal Morphological Remodeling After Intragastric Apelin-13 Administration in Unweaned Rats

## TL;DR

Giving apelin-13 to newborn rats changes the structure of their stomach and intestines, affecting cell size, mucus production, and hormone levels, which could help improve neonatal nutrition.

## Contribution

This study is the first to show apelin-13's effects on gut development, including mucosal remodeling, nerve networks, and appetite hormone expression in unweaned rats.

## Key findings

- Apelin-13 increased gastric mucosal thickness and altered zymogen cell size in newborn rats.
- The small intestine showed a regional remodeling pattern, with stronger effects in the upper part.
- Apelin-13 changed ghrelin and leptin levels, indicating its role in appetite regulation during early development.

## Abstract

Young mammals rely on rapid growth of the stomach and intestines to transition from milk to solid food, but the hormones that guide this process are still being discovered. One such hormone is apelin, a protein naturally present in the digestive tract and in milk. We asked whether giving apelin directly into the stomach of newborn rats would change how their stomach and small intestine develop. Ten-day-old rat pups received apelin or placebo for two weeks, after which we examined the tissues and measured the thickness of the gut wall, the size of surface cells that absorb nutrients, the mucus-producing cells that protect the lining, and the structure of nerve networks inside the gut that control movement. We also measured two appetite-related hormones made in the gut, ghrelin, and leptin. Apelin made the stomach lining thicker and changed some digestive cells, and it reshaped the small intestine depending on the region, with stronger effects in the upper part. The gut nerve networks and local ghrelin and leptin signals also changed. These findings show that apelin can influence early digestive development and may help explain how feeding hormones program gut function in infancy, which could be useful for improving neonatal nutrition.

Apelin is a postnatal peptide implicated in gastrointestinal maturation, yet its combined effects on mucosa, enteric plexuses, and gut-derived appetite signals are not well defined. We investigated the impact of chronic intragastric apelin-13 on the stomach and small intestine of unweaned rats. Twelve Wistar pups of both sexes received apelin-13 (100 nmol/kg body weight, twice daily) or saline from postnatal day 10 for 14 days. After euthanasia, gastric and small-intestinal samples were processed for histomorphometry, neurofilament immunohistochemistry of myenteric and submucosal plexuses, and quantitative staining for ghrelin and leptin. Apelin-13 increased gastric mucosal thickness and pit and gland height, enlarged zymogen cells, and reduced muscularis propria thickness, while leaving submucosa and parietal cell area unchanged. In the small intestine, apelin produced a clear proximal-distal gradient, with enhanced villus-mucosa indices proximally and reduced indices in mid-to-distal jejunum, alongside broader crypt remodeling. Enterocyte and goblet cell dimensions changed in parallel with these regional shifts. Myenteric and submucosal ganglia were also remodeled in a segment-dependent manner. Ghrelin immunoreactivity increased in most regions, whereas leptin showed opposite proximal and distal responses. Overall, early-life luminal apelin-13 reshapes gastric and intestinal architecture and local hormone expression.