Reversal of diabetic nephropathy by a ketogenic diet.
Reversal of diabetic nephropathy by a ketogenic diet.
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DOI：
10.1371/journal.pone.0018604
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发表时间：
2011-04-20
期刊：
影响因子：
3.7
通讯作者：
Mobbs CV
中科院分区：
文献类型：
--
作者：
Poplawski MM;Mastaitis JW;Isoda F;Grosjean F;Zheng F;Mobbs CV
强化胰岛素治疗和限制蛋白质摄入可延缓多种情况下肾病的发展，但已知可逆转肾病的干预措施很少。最近观察到酮3-β-羟基丁酸（3-OHB）降低了对葡萄糖的分子反应，我们假设生酮饮食可以延长3-OHB的升高，可能会逆转糖尿病引起的病理过程。为了解决这一假设，我们评估了长期维持生酮饮食是否会逆转糖尿病引起的肾病。在1型（秋田）和2型（db/db）糖尿病的小鼠模型中，允许发展糖尿病肾病（如白蛋白尿所示），然后将一半小鼠转换为生酮饮食。喂食8周后，处死小鼠以评估基因表达和组织学。糖尿病肾病，如白蛋白/肌酐比值以及应激诱导基因的表达所示，通过生酮饮食维持2个月完全逆转。然而，肾病的组织学证据仅部分逆转。这些研究表明，糖尿病肾病可以通过相对简单的饮食干预逆转。葡萄糖代谢降低是否介导生酮饮食的保护作用仍有待确定。
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.
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