Ghrelin treatment and exercise improve sperm quality in rats fed an obesogenic diet:A potential link to LEAP2

This study aimed to evaluate whether ghrelin, with or without exercise, can reverse the alterations caused by an obesogenic diet on sperm quality, metabolism, and endocrine profile with emphasis on LEAP2 levels. Fifty five male Wistar rats were randomly assigned, from weaning to postnatal day (pnd) 103, to five groups (n = 11/group): CD (standard chow + water); ObD (chow enriched with 30 % pork fat + water with 5 % fructose); ObD + ghrelin (obesogenic diet + 6 nmol/animal/day of ghrelin from pnd 85); ObD + Exc (obesogenic diet + standardized exercise in a running wheel, 15 min/day, 3 days/week); and ObD + ghrelin + Exc. Body weight gain was accelerated in ObD, but ghrelin and/or Exc slowed it down. At pnd 103, all treatment groups were significantly lighter than the ObD group. Metabolic parameters were impaired in ObD animals, with exercise markedly improving them, reducing cholesterol and triglyceride levels close to control values, while ghrelin exerted a modest effect, partially reducing triglycerides and the triglyceride/HDL index but leaving values still dysregulated. Sperm concentration and motility were significantly reduced in the ObD vs. CD; ghrelin and/or Exc completely reversed these detrimental effects. Plasma LEAP2 was significantly higher in the animals receiving the obesogenic diet, and, LEAP2 correlated inversely with sperm concentration, explaining 22 % of its variation. No synergistic effects were found between ghrelin and Exc. We demonstrated for the first time the potential of ghrelin to reverse sperm quality alterations secondary to obesity. Furthermore, ghrelin exhibited weight gain-slowing effects comparable to those of Exc. We also found an association between LEAP2 and sperm concentration, which warrants further investigation.