Warner Gina, Hein Kyaw Zaw, Nin Veronica, Edwards Marika, Chini Claudia C S, Hopp Katharina, Harris Peter C, Torres Vicente E, Chini Eduardo N
Department of Anesthesiology, Robert and Arlene Kogod Center on Aging, and.
Department of Anesthesiology, Robert and Arlene Kogod Center on Aging, and
J Am Soc Nephrol. 2016 May;27(5):1437-47. doi: 10.1681/ASN.2015020132. Epub 2015 Nov 4.
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the accumulation of kidney cysts that ultimately leads to loss of renal function and kidney failure. At present, the treatment for ADPKD is largely supportive. Multiple studies have focused on pharmacologic approaches to slow the development of the cystic disease; however, little is known about the role of nutrition and dietary manipulation in PKD. Here, we show that food restriction (FR) effectively slows the course of the disease in mouse models of ADPKD. Mild to moderate (10%-40%) FR reduced cyst area, renal fibrosis, inflammation, and injury in a dose-dependent manner. Molecular and biochemical studies in these mice indicate that FR ameliorates ADPKD through a mechanism involving suppression of the mammalian target of the rapamycin pathway and activation of the liver kinase B1/AMP-activated protein kinase pathway. Our data suggest that dietary interventions such as FR, or treatment that mimics the effects of such interventions, may be potential and novel preventive and therapeutic options for patients with ADPKD.
常染色体显性多囊肾病(ADPKD)是一种遗传性疾病,其特征是肾囊肿的积累,最终导致肾功能丧失和肾衰竭。目前,ADPKD的治疗主要是支持性的。多项研究集中在减缓囊性疾病发展的药物治疗方法上;然而,关于营养和饮食控制在多囊肾病中的作用知之甚少。在此,我们表明食物限制(FR)可有效减缓ADPKD小鼠模型的疾病进程。轻度至中度(10%-40%)的食物限制以剂量依赖的方式减少了囊肿面积、肾纤维化、炎症和损伤。对这些小鼠的分子和生化研究表明,食物限制通过一种涉及抑制雷帕霉素哺乳动物靶点途径和激活肝激酶B1/AMP激活蛋白激酶途径的机制改善ADPKD。我们的数据表明,饮食干预如食物限制,或模拟此类干预效果的治疗,可能是ADPKD患者潜在的新型预防和治疗选择。