Hyperphagia of pregnancy and lactation is associated with changes in appetite-regulating hormones and gastrointestinal modifications in Wistar rats

Abstract

Pregnancy and lactation result in increasing maternal appetite and adiposity, which in humans may lead to long-term weight retention. Previous studies in this area are limited, but some suggest that the appetite-inhibiting (anorexigenic) gut hormone peptide-YY (PYY) is increased in lactation, despite hyperphagia. This work characterised changes in appetite-stimulating (orexigenic) ghrelin and anorexigenic PYY and glucagon-like peptide-1 (GLP-1) and gut architecture during pregnancy and lactation. Female Wistar rats, kept under reverse lighting (lights off 11.00-23.00 hr), were sampled during the dark phase at pregnancy days 4, 12 and 18 and lactation days 0, 5, 10 and 25. Peptides were measured in matched fed and fasted plasma and in gut tissue using radioimmunoassay. Detailed gut measurements were standardised by free-floating tissue and maximal relaxation with nicardipine and were used to determine how gut architecture may change in relation to enteroendocrine cell density and/or peptide concentration. Enteroendocrine cells were quantified using immunofluorescence. Fasted plasma ghrelin during pregnancy was significantly (F(2, 18)=3.767, P=0.043) highest in day 4 pregnant dams and significantly (F(3, 24)=4.546, P=0.012) increased by day 25 of lactation. Ghrelin-immunoreactive stomach cells were significantly (F(2, 17)=29.735, P<0.001) increased at day 0 of lactation (d0L) compared with day 12 pregnant and proestrus controls, and stomach tissue ghrelin concentration was also significantly (Kruskal- Wallis, χ2=10.057, 3 df, P=0.018) increased at d0L. These results suggest that increased ghrelin supported the onset of lactation-associated hyperphagia. Significantly increased GLP-1 and PYY levels in colon tissue during early lactation were associated with significantly increased gastrointestinal size at this time, not satiety. GLP-1 in fed plasma (F(3, 21)=5.505, P=0.006) and both ascending colon PYY (F(3, 22)=4.638, P=0.012) and GLP-1 (F(3, 22)=4.164, P=0.018) levels were significantly reduced in late lactation, also supportive of the marked hyperphagia of late lactation by a reduction in satiety.