Calorie restriction or starvation (fasting) has some beneficial effects on prolongation of life and increased resistance to stress. Calorie restriction has also been shown to have a protective role during ischemia-reperfusion injury (IRI) in several organs, but the underlying causal mechanism has not been elucidated. In this study we investigated the roles and mechanisms of short-term starvation (STS) on liver IRI. Using a warm liver IRI model, we showed that STS significantly attenuates IR-induced liver injury, as evidenced by inhibition of serum aminotransferase levels, improving pathological damage, and decreasing hepatocellular apoptosis, especially 2- or 3-day starvation. Furthermore, we found that 2- or 3-day starvation induced expression of hepatocellular autophagy in vivo and in vitro. Further experiments supported the notion that STS-induced autophagy plays a key role during starvation-regulating protection against liver IRI by autophagy inhibitor (3-methyladenine) intervention. Interestingly, Sirt1, as a longevity gene, was also significantly up-regulated in liver tissues after STS. Importantly, inhibition of Sirt1 using a Sirt1 inhibitor (Sirtinol) abolished STS-induced autophagy and further abrogated STS-mediated protection against liver IRI. In Conclusion, our results demonstrated that STS attenuates liver IRI via the Sirt1-autophagy pathway. Our findings provide the rationale for a novel therapeutic strategy and mechanism for managing liver IRI.

CITATION INFORMATION: Rao J, Zhou H, Zhang F, Wang X, Zhai Y, Lu L. Short-Term Starvation Attenuates Liver Ischemia Reperfusion Injury by SIRT1-Autophagy Signaling in Mice. Am J Transplant. 2016;16 (suppl 3).

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