Leptin Intake at Physiological Doses Throughout Lactation in Male Wistar Rats Normalizes the Decreased Density of Tyrosine Hydroxylase-Immunoreactive Fibers in the Stomach Caused by Mild Gestational Calorie Restriction

Abstract

Introduction: Gestational under nutrition in rats has been shown to decrease expression of sympathetic innervation markers in peripheral tissues of offspring, including the stomach. This has been linked to lower gastric secretion and decreased circulating levels of ghrelin. Considering the critical role of leptin intake during lactation in preventing obesity and reversing adverse developmental programming effects, we aimed to find out whether leptin supplementation may reverse the above mentioned alterations caused by mild gestational calorie restriction. Methods: Three groups of male rats were studied at a juvenile age (25 days old) and during adulthood (3 and 6 months old): the offspring of ad libitum fed dams (controls), the offspring of dams that were diet restricted (20%) from days 1 to 12 of gestation (CR), and CR rats supplemented with a daily oral dose of leptin (equivalent to 5 times the average amount they could receive each day from maternal milk) throughout lactation (CR-Leptin). The density of TyrOH-immunoreactive (TyrOH(+)) fibers and the levels of Tyrosine hydroxylase (TyrOH)-used as potential markers of functional sympathetic innervationwere measured in stomach. Plasma leptin and ghrelin levels were also determined. Results: Twenty five-day-old CR rats, but not CR-Leptin rats, displayed lower density of TyrOH(+) fibers (-46%) and TyrOH levels (-47%) in stomach compared to controls. Alterations in CR animals were mitigated at 6 months of age, and differences were not significant. Adult CR-Leptin animals showed higher plasma ghrelin levels than CR animals, particularly at 3 months (+16%), and a lower leptin/ghrelin ratio (-28 and -37% at 3 and 6 months, respectively). Conclusion: Leptin intake during lactation is able to reverse the alterations in the density of TyrOH(+) fibers in the stomach and normalize the increased leptin/ghrelin ratio linked to a mild gestational calorie restriction in rats, supporting the relevance of leptin as an essential nutrient during lactation.