title: Reversal of diabetic nephropathy by a ketogenic diet.
abstract: Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined.
authors.affiliation: Fishberg Center for Neurobiology, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Michal M
authors.initials: MM
authors.lastname: Poplawski
authors.forename: Jason W
authors.initials: JW
authors.lastname: Mastaitis
authors.forename: Fumiko
authors.initials: F
authors.lastname: Isoda
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Grosjean
authors.forename: Feng
authors.initials: F
authors.lastname: Zheng
authors.forename: Charles V
authors.initials: CV
authors.lastname: Mobbs
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000178:diet therapy*; D055423:Diet, Ketogenic; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL