[摘要]：Numerous steatotic livers are discarded for transplantation because of their poor tolerance of ischemia-reperfusion (I/R). The injurious effects of retinol-binding protein 4 (RBP4) in various pathologies are well documented. RBP4 levels are reduced by peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists. Strategies aimed at increasing PPAR gamma protect steatotic livers under warm ischemia. Ischemic preconditioning (PC) based on brief periods of I/R protects steatotic liver grafts against I/R injury, but the responsible mechanism is poorly understood. We examined the roles of RBP4 and PPAR gamma in I/R injury associated with steatotic liver transplantation and the benefits of PC in such situations. We report that RBP4 and PPAR gamma expression levels in nonsteatotic livers were similar to those found in the sham group. However, reduced RBP4 and increased PPAR gamma levels were observed in steatotic livers. Treatment with either RBP4 or a PPAR gamma antagonist was effective only in steatotic livers. PC, which increased RBP4 levels, and RBP4 treatment both reduced PPAR gamma levels and hepatic injury in steatotic livers. When PPAR gamma was activated, neither RBP4 treatment nor PC (despite RBP4 induction) protected steatotic livers. In conclusion, steatotic liver grafts are more predisposed to down-regulate RBP4 and overexpress PPAR gamma. RBP4 treatment and PC, through RBP4 induction, reduced PPAR gamma levels in steatotic liver grafts, thus protecting them from the PPAR gamma detrimental effects.
