The activation of PGC-1α protects the liver from IR damage

Abstract

The study is focused on an important clinical problem, liver transplant. The number of donor livers is insufficient to cover the needs for liver transplants, which drives the use of suboptimal livers, like those that have an important accumulation of fat (fatty liver/ steatotic liver). The steatosis makes the liver more sensitive to the damage that results from the ischemia-reperfusion process (IR) but also makes it less responsive to preconditioning protocols that normally make the livers more resistant to IR damage. Our study shows that PGC-1α in response to IR is necessary to protect the liver from IR damage and mediates the activation of protection mechanisms following the ischemic preconditioning protocol. It also suggests that the reduced activity of PGC-1α in the steatotic liver could be responsible for its increased sensitivity to IR damage and poor response to preconditioning protocols. These observations allow us to propose PGC-1α as a relevant therapeutic target whose activation in the donor livers, could facilitate the clinical use of steatotic livers for transplantation. Therefore, we believe this study has adequately addressed the objectives initially proposed and it has identified PGC-1α as a key element in hepatic physiology, providing relevant insight into the mechanisms involved and opening new therapeutic venues.