A kidney specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy

Cycles of a fasting-mimicking diet (FMD) promote regeneration and reduce damage in the pancreas, blood, gut, and nervous systems of mice but its effect on kidney disease is unknown, and the FMD has not been tested in rats. Here we show that cycles of a newly developed low-salt FMD (LS-FMD) restore normal proteinuria, nephron structure and function in rats with puromycin-induced nephrosis in the long term. LS-FMD induces expression of nephrogenic markers, resembling renal developmental processes in multiple kidney structures, and activates podocyte-lineage reprogramming pathways, in addition to promoting a quiescent state in mature podocytes.禁食模拟饮食（fasting-mimicking diet, FMD）周期可促进小鼠胰腺、血液、肠道及神经系统的再生并减轻组织损伤，但该饮食对肾脏疾病的影响尚未明确，且此前尚未在大鼠中开展相关测试。本研究证实，一款新开发的低盐禁食模拟饮食（low-salt FMD, LS-FMD）可长期恢复嘌呤霉素诱导性肾病大鼠的正常蛋白尿水平、肾单位结构与功能。LS-FMD可诱导肾源性标志物的表达，在多种肾脏结构中重现肾脏发育进程，并激活足细胞谱系重编程通路，此外还可促进成熟足细胞进入静息状态。