Sex differences in gut satiety hormones peptide-YY and glucagon-like peptide-1 in pups raised in larger lactation litter sizes

Introduction: Previous studies have established that the size of litters during lactation influences body size and adiposity in male rat pups. Levels of gut hormones such as appetite-stimulating ghrelin and appetite-reducing peptide-YY (PYY) and glucagon-like peptide-1 (GLP-1) have not been examined in this model despite an increased susceptibility to obesity into adulthood. This study aimed to establish whether changes in gut appetite hormones, resulting from lactation litter size, could contribute to the increased risk of adulthood obesity. Methods: Male and female littermates from small (n=4), control (n=8) and large (n=12) litter sizes were studied at weaning age (25 days), with litter sizes adjusted prior to 1 day postpartum; pups remained with the dams throughout the study. Stomach ghrelin and colonic PYY and GLP-1 were quantified using radioimmunoassay. Stomachs were emptied, blotted dry and weighed. Body length was taken from between the front paws to the anus. Results and Discussion: No differences were found in stomach ghrelin levels between the pups, but levels of the gut satiety hormones PYY and GLP-1 were found to be altered in colon tissue. In descending colon, PYY and GLP-1 concentrations were significantly lower in male, but not female, pups from the large litters. Physically, both the male and female pups fed in the large litters were significantly shorter and lighter and had significantly lighter stomach tissue. We suggest that the significantly smaller male pups may have had reduced satiety as a mechanism to achieve ‘catch-up growth’ into adulthood. It is unclear whether females may show similar adaptations at a later stage. This study further demonstrated differences between young males and females, with differences evident even before sexual maturation. This work highlights the importance of standardising litter size as early as possible, especially in studies of appetite control.