Ghrelin signalling is dysregulated in male but not female offspring in a rat model of maternal vertical sleeve gastrectomy.

Abstract

Bariatric surgery is the most effective and durable means of treating obesity and its comorbidities. Women make up 80% of those receiving weight loss surgery and they experience improvements in fertility. Unfortunately, bariatric surgery in the context of pregnancy is associated with complications, including growth restriction and small-for-gestational age offspring (SGA). SGA offspring have a greater risk for obesity in adulthood, although the mechanism for this SGA-induced obesity is unknown. In a rat model of vertical sleeve gastrectomy (VSG), we previously identified reductions during pregnancy in ghrelin, a stomach-derived hormone that increases appetite and induces growth hormone secretion. Here, we hypothesise that VSG offspring will have altered ghrelin signalling compared to offspring of Sham dams as a result of reduced in utero ghrelin. At postnatal day (PND)21, male and female offspring of dams that have previously received VSG have an increase in mRNA expression for the ghrelin receptor in the hypothalamus compared to Sham offspring, and the expression of GOAT is lower in females compared to males. Liver expression of endogenous ghrelin antagonist, LEAP2, is elevated at PND60 in VSG offspring. Expression of other genes in the growth hormone system (growth hormone-releasing hormone and growth hormone) were not altered. Plasma levels of total ghrelin at PND21 are also not different between VSG and Sham pups. In adult pups, 1-hour chow intake of male but not female VSG offspring given is less than Sham offspring when given 50µgkg-1 of exogenous ghrelin by i.p. injection. These results indicate that maternal VSG surgery has an impact on ghrelin signalling in offspring and that, as adults, male VSG offspring may be functionally less responsive to ghrelin than controls.