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Cell Metab. 2019 Dec 3;30(6):1007-1023.e5. doi: 10.1016/j.cmet.2019.09.012. Epub 2019 Oct 17.

Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease.

Author information

1
Molecular, Cellular, and Developmental Biology, and Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA.
2
Department of Veterinary Medicine & Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA.
3
Division of Nephrology, University of Alabama and the Department of Veterans Affairs Medical Center, Birmingham, AL, USA.
4
Molecular, Cellular, and Developmental Biology, and Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA. Electronic address: weimbs@ucsb.edu.

Abstract

Mild reduction in food intake was recently shown to slow polycystic kidney disease (PKD) progression in mouse models, but whether the effect was due to solely reduced calories or some other aspect of the diet has been unclear. We now show that the benefit is due to the induction of ketosis. Time-restricted feeding, without caloric reduction, strongly inhibits mTOR signaling, proliferation, and fibrosis in the affected kidneys in a PKD rat model. A ketogenic diet had a similar effect and led to regression of renal cystic burden. Acute fasting in rat, mouse, and feline models of PKD results in rapid reduction of cyst volume, while oral administration of the ketone β-hydroxybutyrate (BHB) in rats strongly inhibits PKD progression. These results suggest that cystic cells in PKD are metabolically inflexible, which could be exploited by dietary interventions or supplementation with BHB, representing a new therapeutic avenue to treat PKD.

KEYWORDS:

beta-hydroxybutyrate; ketogenic diet; ketosis; metabolic inflexibility; polycystic kidney disease

PMID:
31631001
DOI:
10.1016/j.cmet.2019.09.012

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