Altered Gene Expressions of Ghrelin, PYY, and CCK in the Gastrointestinal Tract of the Hyperphagic Intrauterine Growth Restriction Rat Offspring

Abstract

Intrauterine growth restriction (IUGR) is associated with a substantially greater incidence of metabolic syndrome in adulthood. Animal studies have shown that IUGR offspring are hyperphagic during the early postnatal period and therefore exhibit obesity. The molecular mechanisms underlying food intake regulation in the gastrointestinal tract have not been clarified in IUGR. In the present study, we utilized a rat model of IUGR by restricting the food intake of the mother (50% of the normal intake, ad libitum; FR group) from day 7 of gestation until delivery. Pups from undernourished mothers were fostered by control mothers. We examined the food intake and assessed the gene expressions of ghrelin, peptide YY (PYY), and cholecystokinin (CCK) in the alimentary tract of male newborns (postnatal day1) and adult offspring (age, 7 months). Compared to the offspring whose mothers received the standard diet ad libitum (CON offspring), FR offspring were hyperphagic from the weaning time until the end of the experiment, and resulted in a heavier final weight. Both newborn and adult FR offspring had higher ghrelin gene expression in the stomach and higher ghrelin plasma levels than did the controls. Although the gastrointestinal gene expressions and plasma levels of the anorexic peptides, PYY and CCK, were elevated in the FR newborns, they decreased in the FR adults. Our findings suggest that the altered gene expressions of orexigenic and anorexigenic gut peptides in the gastrointestinal tract in the maternal undernutrition-induced IUGR offspring provide a potential mechanism to explain hyperphagia and obesity seen in these offspring.

Early growth and postprandial appetite regulatory hormone responses

“…It has been suggested that prenatal growth as well as growth during early infancy may influence the appetite regulatory system by programming appetite regulatory hormones, such as an orexigenic (ghrelin) and an anorexigenic (peptide tyrosine-tyrosine; PYY). Animal studies have supported this hypothesis, showing that postnatal growth retardation has an effect on appetite regulation ( 7 – 9 ) and that the prevention of immediate rapid newborn catch-up growth may reduce the risk of obesity ( 10 , 11 ) . In addition, an epidemiological study of young adolescents has found an association between rapid early growth and the elevated fasting concentration of ghrelin ( 12 ) .…”

Loss of Vagal Sensitivity to Cholecystokinin in Rats Born with Intrauterine Growth Retardation and Consequence on Food Intake

“…We first hypothesized that gene expression as well as the basal and postprandial release of those peptides may be altered in LP rats. A previous study reported elevated plasma ghrelin and reduced CCK and PYY in adult IUGR rats obtained by a 50%-caloric restriction of their dams diet during gestation and maintained restricted during lactation (37). These changes were paralleled to mRNA levels in gastric and intestinal tissues.…”

Neuroendocrine regulation of appetitive ingestive behavior

“…Therefore, increased postnatal ghrelin likely plays a role in the rapid catch-up growth observed in most models of gestational programming. In rodents, 50% maternal food restriction during the second half of gestation results in LBW pups that, like human LBW infants, have significantly increased ghrelin expression (Cortelazzi et al, 2003 ; Nagata et al, 2011 ). These animals develop hyperphagia and obesity and demonstrate that catch-up growth among LBW offspring results in programmed elevation of plasma ghrelin levels (reviewed by Breton, 2013 ).…”