title: Short-term starvation attenuates liver ischemia-reperfusion injury (IRI) by Sirt1-autophagy signaling in mice.
abstract: Calorie restriction or starvation (fasting) has some beneficial effects in terms of prolonging life and increasing resistance to stress. It has also been shown that calorie restriction has a protective role during ischemia-reperfusion injury (IRI) in several organs, but the underlying mechanism has not been elucidated. In this study we investigated the effects and molecular mechanisms of short-term starvation (STS) on liver IRI in a mouse liver IRI model. We found that STS significantly attenuated liver IRI in this model, as evidenced by inhibition of serum aminotransferase levels, and decreased pathological damage and hepatocellular apoptosis, especially after 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 provided support for the notion that STS-induced autophagy played a key role during starvation-regulated protection against liver IRI via autophagy inhibition with 3-methyladenine. Interestingly, the longevity gene Sirt1 was also significantly up-regulated in liver after STS. Importantly, inhibition of Sirt1 by sirtinol abolished STS-induced autophagy and further abrogated STS-mediated protection against liver IRI. In conclusion, our results indicate that STS attenuates liver IRI via the Sirt1-autophagy pathway. Our findings provide a rationale for a novel therapeutic strategy for managing liver IRI.
authors.affiliation: Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University Nanjing 210029, Jiangsu, PR China.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Qin
authors.affiliation: Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University Nanjing 210029, Jiangsu, PR China.
authors.forename: Junjin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University Nanjing 210029, Jiangsu, PR China.
authors.forename: Xinzheng
authors.initials: X
authors.lastname: Dai
authors.affiliation: Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University Nanjing 210029, Jiangsu, PR China.
authors.forename: Haoming
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University Nanjing 210029, Jiangsu, PR China.
authors.forename: Xiongxiong
authors.initials: X
authors.lastname: Pan
authors.affiliation: Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical University Nanjing 210029, Jiangsu, PR China.
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical UniversityNanjing 210029, Jiangsu, PR China; Translational Medicine Research Center of Jiangning Hospital, Nanjing Medical UniversityNanjing 210029, Jiangsu, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical UniversityNanjing 210029, Jiangsu, PR China; Translational Medicine Research Center of Jiangning Hospital, Nanjing Medical UniversityNanjing 210029, Jiangsu, PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Rao
authors.affiliation: Liver Transplantation Center of First Affiliated Hospital, Nanjing Medical UniversityNanjing 210029, Jiangsu, PR China; Translational Medicine Research Center of Jiangning Hospital, Nanjing Medical UniversityNanjing 210029, Jiangsu, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
keywords: Short-term starvation; Sirt1; autophagy; ischemia reperfusion injury; liver