Dietary or pharmacological inhibition of insulin-like growth factor-1 protects from renal ischemia-reperfusion injury in mice

  • iScience. 2024 Oct 28;27(12):111256. doi: 10.1016/j.isci.2024.111256.
Arnaud Lyon  1  2  3  4 ,  Thomas Agius  1  3  4 ,  Michael R Macarthur  5 ,  Kevin Kiesworo  1 ,  Louis Stavart  1  2 ,  Florent Allagnat  1 ,  Sarah J Mitchell  6 ,  Leonardo V Riella  4 ,  Korkut Uygun  3  4 ,  Heidi Yeh  3  4 ,  Sebastien Déglise  1 ,  Déla Golshayan  2 ,  Alban Longchamp  1  3  4
Affiliations
  • 1. Department of Vascular Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.
  • 2. Transplantation Center and Transplantation Immunopathology Laboratory, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.
  • 3. Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • 4. Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • 5. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
  • 6. Ludwig Princeton Branch, Princeton University, Princeton, NJ, USA.
PMID: 39759002 DOI: 10.1016/j.isci.2024.111256
Abstract

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.

Keywords
Biochemistry; Biological sciences; Cellular physiology; Natural sciences; Pharmacology; Physiology.
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