Investigation of ghrelin-mediated effects of chronic intermittent fasting on gastrointestinal motor functions

Objective: This study aims to investigate the ghrelinergic system–mediated effects of an intermittent fasting feeding model on the gastrointestinal system in rats. Method: In this study, twenty male Sprague–Dawley rats were used; ten served as controls and ten were subjected to a 14-day intermittent fasting (IF) diet. Contractile and relaxant responses of gastrointestinal tissues (ileum and fundus) were evaluated using an organ bath system. Bethanechol was applied to assess contraction, sodium nitroprusside (SNP) to assess relaxation, and electrical field stimulation (EFS) was used to probe neural activity. Gastrointestinal transit (GIT) and solid gastric emptying were also measured. Total ghrelin levels in plasma and GI tissues were analyzed by ELISA, and protein expression was compared between groups using Western blotting. Results: Under intermittent fasting, body weight decreased while food intake normalized to body weight increased; solid gastric emptying and total gastrointestinal transit were accelerated. Plasma ghrelin levels were unchanged, whereas at the tissue level fundic ghrelin and ileal GHSR signals showed a tendency to increase. In organ bath assays, the spontaneous contraction frequency in the fundus was maintained but increased in the ileum; the motility index was similar between groups in both tissues. Bethanechol increased contractions in a concentration-dependent manner, and the GHSR antagonist reduced responses at higher concentrations; sodium nitroprusside produced pronounced relaxation in the fundus and limited relaxation in the ileum. For EFS-evoked contractions, no group difference was observed in the fundus, whereas responses were greater at higher frequencies in the intermittent fasting group in the ileum; no group differences were detected for EFS-evoked relaxation. Conclusion: This study suggests that chronic intermittent fasting in rats increases enteric ghrelin expression, thereby stimulating gastrointestinal motility, and points to a potential complementary therapeutic approach for gastrointestinal motor dysfunction. Key words: intermittent fasting, gastrointestinal system, ghrelin, isolated organ bath