Lyon Arnaud, Agius Thomas, Macarthur Michael R, Kiesworo Kevin, Stavart Louis, Allagnat Florent, Mitchell Sarah J, Riella Leonardo V, Uygun Korkut, Yeh Heidi, Déglise Sebastien, Golshayan Déla, Longchamp Alban
Department of Vascular Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.
Transplantation Center and Transplantation Immunopathology Laboratory, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.
iScience. 2024 Oct 28;27(12):111256. doi: 10.1016/j.isci.2024.111256. eCollection 2024 Dec 20.
One-week protein restriction (PR) limits ischemia-reperfusion (IR) damages and improves metabolic fitness. Similarly, longer-term calory restriction results in increased lifespan, partly via reduced insulin-like growth factor (IGF)-1. However, the influence of short-term PR on IGF-1 and its impact on IR are unknown. PR was achieved in mice via one-week carbohydrate loading and/or through a low-protein diet. PR decreased IGF-1 circulating levels as well as renal and hepatic expression. Upon renal IR, serum IGF-1 positively correlated with renal dysfunction and tissular damages, independently of sex and age. Exogenous IGF-1 administration abrogated PR benefits during IR, while IGF-1 receptor inhibition with linsitinib was protective. IGF-1 was associated with a reduction in forkhead box O (FoxO), and AMP-activated protein kinase (AMPK) signaling pathways previously demonstrated to improve IR resilience in various organs. These data support dietary or pharmacological reduction of IGF-1 signaling to mitigate IR injury prior to solid organ transplantation and beyond.
为期一周的蛋白质限制（PR）可限制缺血再灌注（IR）损伤并改善代谢适应性。同样，长期的热量限制会延长寿命，部分原因是胰岛素样生长因子（IGF）-1减少。然而，短期PR对IGF-1的影响及其对IR的作用尚不清楚。通过一周的碳水化合物负荷和/或低蛋白饮食在小鼠中实现PR。PR降低了循环中IGF-1的水平以及肾脏和肝脏中的表达。在肾脏IR时，血清IGF-1与肾功能障碍和组织损伤呈正相关，与性别和年龄无关。外源性给予IGF-1消除了IR期间PR的益处，而用林西替尼抑制IGF-1受体则具有保护作用。IGF-1与叉头框O（FoxO）和AMP活化蛋白激酶（AMPK）信号通路的减少有关，先前已证明这些信号通路可改善各种器官的IR恢复力。这些数据支持在实体器官移植之前及之后通过饮食或药物降低IGF-1信号传导以减轻IR损伤。
