biostudies-literature00530Hopp KNCATSNIDDK NIH HHSNCRR NIH HHSUniversity of Colorado Denver Colorado Clinical and Translational Sciences InstitutePKD FoundationNCI NIH HHSNIHNIDDKNIH HHS103697https://www.ebi.ac.uk/biostudies/studies/S-EPMC8760407biostudies-literatureUnknown25(1)Progression of autosomal dominant polycystic kidney disease (ADPKD) is modified by metabolic defects and obesity. Indeed, reduced food intake slows cyst growth in preclinical rodent studies. Here, we demonstrate the feasibility of daily caloric restriction (DCR) and intermittent fasting (IMF) in a cohort of overweight or obese patients with ADPKD. Clinically significant weight loss occurred with both DCR and IMF; however, weight loss was greater and adherence and tolerability were better with DCR. Further, slowed kidney growth correlated with body weight and visceral adiposity loss independent of dietary regimen. Similarly, we compared the therapeutic efficacy of DCR, IMF, and time restricted feeding (TRF) using an orthologous ADPKD mouse model. Only ADPKD animals on DCR lost significant weight and showed slowed cyst growth compared to <i>ad libitum</i>, IMF, or TRF feeding. Collectively, this supports therapeutic feasibility of caloric restriction in ADPKD, with potential efficacy benefits driven by weight loss.iScienceWeight loss and cystic disease progression in autosomal dominant polycystic kidney disease.PMC8760407P30 DK048520P30 DK090868P30 CA046934R03 DK129414K01 DK114164S10 OD023485R03 DK118215K01 DK103678T32 DK007135S10 OD018435UL1 RR025780Poudyal BChonchol MNguyen DTYou ZMiller MSerkova NJNowak KLJackman MRJohnson GCBing KSteele CNCatenacci VADwivedi NWang WNemenoff RAKline TLMacLean PSGitomer BHopp K53falseWeight loss and cystic disease progression in autosomal dominant polycystic kidney disease.Progression of autosomal dominant polycystic kidney disease (ADPKD) is modified by metabolic defects and obesity. Indeed, reduced food intake slows cyst growth in preclinical rodent studies. Here, we demonstrate the feasibility of daily caloric restriction (DCR) and intermittent fasting (IMF) in a cohort of overweight or obese patients with ADPKD. Clinically significant weight loss occurred with both DCR and IMF; however, weight loss was greater and adherence and tolerability were better with DCR. Further, slowed kidney growth correlated with body weight and visceral adiposity loss independent of dietary regimen. Similarly, we compared the therapeutic efficacy of DCR, IMF, and time restricted feeding (TRF) using an orthologous ADPKD mouse model. Only ADPKD animals on DCR lost significant weight and showed slowed cyst growth compared to <i>ad libitum</i>, IMF, or TRF feeding. Collectively, this supports therapeutic feasibility of caloric restriction in ADPKD, with potential efficacy benefits driven by weight loss.2022-01-01T00:00:00Z2022 Jan2024-11-19T22:34:19.005Z2022-02-11T16:16:32.918ZS-EPMC87604073505960710.1016/j.isci.2021.103697