美国加州大学圣芭芭拉分校的Thomas Weimbs课题组取得一项新进展，他们发现了酮症能够改善多囊肾病（PKD）中肾囊肿的生长。2019年10月17日，国际知名学术期刊《细胞—代谢》在线发表了这一成果。

最近的研究显示，食物摄入量的轻微减少会减慢小鼠模型中PKD的进展，但尚不清楚其影响是仅由于卡路里减少还是饮食的其他方面所致。

研究人员发现该益处是由于酮症的诱导。在PKD大鼠模型中，限时进食且无热量减少，可强烈抑制受影响肾脏中的mTOR信号传导、增殖和纤维化。生酮饮食具有相似的作用，并导致肾囊性负担的消退。 大鼠、小鼠和猫的PKD模型的急性禁食可导致囊肿体积迅速减少，而大鼠口服β-羟基丁酸酮（BHB）则可强烈抑制PKD进程。

这些结果表明，PKD中的囊细胞在代谢上缺乏弹性，可以通过饮食干预或补充BHB加以利用，这提示了治疗PKD的新途径。

附：英文原文

Title: Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease

Author: Jacob A. Torres, Samantha L. Kruger, Caroline Broderick, Tselmeg Amarlkhagva, Shagun Agrawal, John R. Dodam, Michal Mrug, Leslie A. Lyons, Thomas Weimbs

Issue&Volume: 17 October 2019

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.

DOI: 10.1016/j.cmet.2019.09.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30515-7