Male and female intrauterine growth-restricted offspring differ in blood pressure, renal function, and glucose homeostasis responses to a postnatal diet high in fat and sugar

Abstract

It is well established that inadequate nutrition during fetal life followed by postnatal overabundance programs adiposity and glucose intolerance. Studies addressing sexual dimorphism in developmental responses to a dietary mismatch are limited; the effect on blood pressure and renal function is understudied. Therefore, this study tested the hypothesis that a mismatch of prenatal and postnatal nutrition heightens cardiorenal and metabolic risk, outcomes that may vary by sex. Male and female offspring from sham-operated (control) or reduced uterine perfusion dams (growth restricted) were fed regular chow or a diet high in fat and sugar (enriched diet) from weaning until 6 months of age. Male and female offspring were assessed separately; 2-way ANOVA was used to investigate interactions between intrauterine growth-restricted and enriched-diet. Blood pressure was increased in all enriched-diet groups but did not differ in enriched-diet male or female growth-restricted versus same-sex control counterparts. Glomerular filtration rate was reduced in male growth-restricted regardless of diet; a decrease exacerbated by the enriched-diet suggesting the pathogenesis of increased blood pressure induced via an enriched-diet differs between male growth-restricted versus male control. An enriched diet was associated with glucose intolerance in male and female control but not male growth-restricted; the enriched diet exacerbated glucose intolerance in female growth-restricted. Thus, these findings indicate male growth-restricted are resistant to impaired glucose homeostasis, whereas female growth-restricted are susceptible to metabolic dysfunction regardless of postnatal diet. Hence, moderation of fat and sugar intake may be warranted in those born low birth weight to ensure minimal risk for chronic disease.