β-hydroxybutyrate recapitulates the beneficial effects of ketogenic metabolic therapy in polycystic kidney disease.

ABSTRACT: Autosomal-dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by the formation of fluid-filled renal cysts, loss of mitochondrial function, decreased fatty acid oxidation, increased glycolysis, and likely renal failure. We previously demonstrated that inducing a state of ketosis ameliorates or reverses PKD progression in multiple animal models. In this study, we compare time-restricted feeding and 48-h periodic fasting regimens in both juvenile and adult Cy/+ rats. Both fasting regimens potently prevent juvenile disease progression and partially reverse PKD in adults. To explore the mechanism of fasting, we administered β-hydroxybutyrate (BHB) to Cy/+ rats and orthologous mouse models of PKD (Pkd1 ^RC/RC , Pkd1-Ksp:Cre). BHB

SUBMITTER: Torres JA 

PROVIDER: S-EPMC11418134 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature