title: Retinol-binding protein 4 and peroxisome proliferator-activated receptor-γ in steatotic liver transplantation.
abstract: 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.
authors.affiliation: Institut d′Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Araní
authors.initials: A
authors.lastname: Casillas-Ramírez
authors.forename: Izabel
authors.initials: I
authors.lastname: Alfany-Fernández
authors.forename: Marta
authors.initials: M
authors.lastname: Massip-Salcedo
authors.forename: M Emília
authors.initials: ME
authors.lastname: Juan
authors.forename: Joana M
authors.initials: JM
authors.lastname: Planas
authors.forename: Anna
authors.initials: A
authors.lastname: Serafín
authors.forename: Mercè
authors.initials: M
authors.lastname: Pallàs
authors.forename: Antoni
authors.initials: A
authors.lastname: Rimola
authors.forename: Juan
authors.initials: J
authors.lastname: Rodés
authors.forename: Carmen
authors.initials: C
authors.lastname: Peralta
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation / Q000379:methods / Q000502:physiology*; D047495:PPAR gamma / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D054839:Retinol-Binding Proteins, Plasma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D047495:PPAR gamma; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma