Increased glucagon-like peptide-1 concentration in rat descending colon during proestrus is associated with decreased food intake at estrus

Johnson, Michelle; Saffrey, Jill and Taylor, Victoria (2013). Increased glucagon-like peptide-1 concentration in rat descending colon during proestrus is associated with decreased food intake at estrus. In: SSR's 46th Annual Meeting Reproductive Health: Nano to Global, 22-26 Jul 2013, Montréal, Québec, Canada, pp. 150–151.



It is well established that whole body energy homeostasis is maintained by numerous circulating hormones and hypothalamic neuropeptides. Ghrelin, produced in the stomach, and peptide-YY (PYY) and glucagon-like peptide-1 (GLP-1), co-secreted from the colon, have been studied in relation to their role as appetite-regulatory hormones. One active area of research is the manipulation of appetite by administering exogenous gut hormones to increase satiety. However, most animal studies have been carried out using males. During the reproductive cycle of female rodents, many studies have shown that estradiol is involved in a decreased food intake between proestrus and estrus. Fewer studies have explored the influence of multiple gut hormones during reproductive states.

The aim of this work was therefore to further elucidate changes in appetite-regulating peptides during the rat estrous cycle. Concentrations of orexigenic (appetite-stimulating) ghrelin and anorexigenic (appetite-inhibiting) PYY and GLP-1 have been quantified in both circulation and in gut tissue. Understanding the mechanisms by which appetite is modulated at each cycle stage may further our understanding of how appetite could be optimally manipulated in females for therapeutic effects.

Nulliparous female Wistar rats were kept under a reverse lighting schedule (lights off 11.00-23.00 hr) and their cycle monitored daily by vaginal lavage. Fed blood samples were obtained 24 hours prior to dissection. Animals were then fasted and dissected at defined stages of the reproductive cycle: proestrus (n=12), estrus (n=11), metestrus (n=9) and diestrus (n=11). Matched fasted blood and gut samples were obtained upon dissection. Hormone concentrations of total peptides in plasma and gut tissue extract were determined using radioimmunoassays.

Mean uterus weight was significantly higher during proestrus (F(3,39)=8.0, P<0.001) than at any other cycle stage and further confirmed proestrus identification. No change in body weight in relation to the cycle was found. Although fasted prior to culling, small amounts of stomach contents (mean=0.6g; range: 0.04-1.8g) were often present. Weight of stomach contents were significantly lower after the transition from proestrus to estrus (F(3,39)=3.2, P=0.034).

Fed and fasted plasma concentrations of ghrelin were not significantly different, however ghrelin in fasted plasma showed a tendency to be lowest during proestrus (P=0.056 ns). Ghrelin concentrations in stomach tissue did not change between cycle stages.

Fed plasma concentrations of PYY (paired t(41)=43.9, P<0.001) and GLP-1 (paired t(42)=5.4, P<0.001) were significantly higher than in fasted plasma, but neither differed significantly with cycle stage. GLP-1 concentration in descending colon tissue was significantly higher at proestrus than during estrus or diestrus (F(3,39)=3.9, P=0.015). Although not significant, PYY in the same tissue showed a tendency for the same pattern of concentrations as GLP-1 throughout the cycle (P=0.079 ns).

In summary, GLP-1 concentration in descending colon was significantly highest at proestrus, associated with a significant decrease in stomach contents at estrus. Observed increases in satiety hormone tissue concentrations, supported by reduced fasted stomach contents during proestrus, could contribute to the reported reduction in food intake at this time during the rat estrous cycle.

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