Retinol binding protein 4 and retinol in steatotic and nonsteatotic rat livers in the setting of partial hepatectomy under ischemia/reperfusion.
Steatotic livers show increased hepatic damage and impaired regeneration after partial hepatectomy (PH) under ischemia/reperfusion (I/R), which is commonly applied in clinical practice to reduce bleeding. The known function of retinol-binding protein 4 (RBP4) is to transport retinol in the circulation. We examined whether modulating RBP4 and/or retinol could protect steatotic and nonsteatotic livers in the setting of PH under I/R. Steatotic and nonsteatotic livers from Zucker rats were subjected to PH (70%) with 60 minutes of ischemia. RBP4 and retinol levels were measured and altered pharmacologically, and their effects on hepatic damage and regeneration were studied after reperfusion. Decreased RBP4 levels were observed in both liver types, whereas retinol levels were reduced only in steatotic livers. RBP4 administration exacerbated the negative consequences of liver surgery with respect to damage and liver regeneration in both liver types. RBP4 affected the mobilization of retinol from steatotic livers, and this revealed actions of RBP4 independent of simple retinol transport. The injurious effects of RBP4 were not due to changes in retinol levels. Treatment with retinol was effective only for steatotic livers. Indeed, retinol increased hepatic injury and impaired liver regeneration in nonsteatotic livers. In steatotic livers, retinol reduced damage and improved regeneration after surgery. These benefits of retinol were associated with a reduced accumulation of hepatocellular fat. Thus, strategies based on modulating RBP4 could be ineffective and possibly even harmful in both liver types in the setting of PH under I/R. In terms of clinical applications, a retinol pretreatment might open new avenues for liver surgery that specifically benefit the steatotic liver.
August Pi i Sunyer Institute for Biomedical Research, Barcelona, Spain.
Maria
M
Elias-Miró
Marta
M
Massip-Salcedo
Jens
J
Raila
Florian
F
Schweigert
Mariana
M
Mendes-Braz
Fernando
F
Ramalho
Mónica B
MB
Jiménez-Castro
Araní
A
Casillas-Ramírez
Raquel
R
Bermudo
Antoni
A
Rimola
Juan
J
Rodes
Carmen
C
Peralta
D000818:Animals; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism* / Q000601:surgery; D006498:Hepatectomy / Q000379:methods*; D007511:Ischemia / Q000150:complications*; D008099:Liver / Q000098:blood supply / Q000378:metabolism* / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051381:Rats; D011924:Rats, Zucker; D015424:Reperfusion / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D014801:Vitamin A / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use
C532035:Rbp4 protein, rat; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A