Abstract
Due to the growing obesity epidemic in the United States, it is now estimated that approximately 1/3 of all children are born to obese moms. These data, coupled with data indicating that obesity is associated with accelerated cyst growth in autosomal dominant polycystic kidney disease (ADPKD) patients, led us to hypothesize that maternal obesity may influence the rate of disease progression in offspring. To test this hypothesis, we induced maternal obesity by high fat diet (HFD) feeding in the orthologous Pkd1RC/RC mouse model of ADPKD and followed polycystic kidney disease (PKD) progression in offspring for up to one year. Surprisingly, and in contrast to our initial hypothesis, exposure to maternal obesity during pregnancy and lactation did not significantly impact PKD severity in offspring at 3 months or one year of age. In contrast, re-exposure to HFD for ~3 months beginning at 12 weeks of age worsened PKD severity in female, but not male, offspring born to obese dams as measured by cystic index, cyst number, and cyst area. Despite worsened cystic parameters, fibrosis and BUN were not altered in these animals. Collectively, these findings indicate that maternal obesity may accelerate PKD severity in female offspring exposed to an obesogenic diet.
Published Version
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