RT Journal Article
SR Electronic
T1 Retinol-Binding Protein 4 and Peroxisome Proliferator-Activated Receptor-γ in Steatotic Liver Transplantation
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 143
OP 153
DO 10.1124/jpet.110.177691
VO 338
IS 1
A1 Araní Casillas-Ramírez
A1 Izabel Alfany-Fernández
A1 Marta Massip-Salcedo
A1 M. Emília Juan
A1 Joana M. Planas
A1 Anna Serafín
A1 Mercè Pallàs
A1 Antoni Rimola
A1 Juan Rodés
A1 Carmen Peralta
YR 2011
UL http://jpet.aspetjournals.org/content/338/1/143.abstract
AB 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-γ (PPARγ) agonists. Strategies aimed at increasing PPARγ 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 PPARγ in I/R injury associated with steatotic liver transplantation and the benefits of PC in such situations. We report that RBP4 and PPARγ expression levels in nonsteatotic livers were similar to those found in the sham group. However, reduced RBP4 and increased PPARγ levels were observed in steatotic livers. Treatment with either RBP4 or a PPARγ antagonist was effective only in steatotic livers. PC, which increased RBP4 levels, and RBP4 treatment both reduced PPARγ levels and hepatic injury in steatotic livers. When PPARγ 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 PPARγ. RBP4 treatment and PC, through RBP4 induction, reduced PPARγ levels in steatotic liver grafts, thus protecting them from the PPARγ detrimental effects.