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Glial cell line–derived neurotrophic factor–induced mice liver defatting: A novel strategy to enable transplantation of steatotic livers
Author(s) -
Taba Taba Vakili Sahar,
Kailar Roshni,
Rahman Khalidur,
Nezami Behtash Ghazi,
Mwangi Simon Musyoka,
Anania Frank A.,
Srinivasan Shanthi
Publication year - 2016
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.24385
Subject(s) - glial cell line derived neurotrophic factor , steatosis , defatting , medicine , endocrinology , liver transplantation , transplantation , oil red o , fatty liver , adipose tissue , neurotrophic factors , chemistry , biochemistry , receptor , disease , adipogenesis
Moderate macrovesicular steatosis (>30%), which is present in almost 50% of livers considered for transplantation, increases the risk of primary graft dysfunction. Our previously published data showed that glial cell line–derived neurotrophic factor (GDNF) is protective against high‐fat diet (HFD)–induced hepatic steatosis in mice. Hence, we hypothesized that perfusion of steatotic livers with GDNF may reduce liver fat content before transplantation. Livers from 8 weeks of regular diet (RD) and of HFD‐fed mice were perfused ex vivo for 4 hours with either vehicle, GDNF, or a previously described defatting cocktail. The liver's residual fat was quantified colorimetrically using a triglyceride (TG) assay kit and by Oil Red O (ORO) and Nile red/Hoechst staining. Liver tissue injury was assessed by using a lactate dehydrogenase (LDH) activity assay. In vitro induction of lipolysis in HepG2 cells was assessed by measuring glycerol and free fatty acid release. ORO staining showed significantly more steatosis in livers from HFD‐fed mice compared with RD‐fed mice ( P < 0.001). HFD livers perfused with GDNF had significantly less steatosis than those not perfused ( P = 0.001) or perfused with vehicle ( P < 0.05). GDNF is equally effective in steatotic liver defatting compared to the defatting cocktail; however, GDNF induces less liver damage than the defatting cocktail. These observations were consistent with data obtained from assessment of liver TG content. Assessment of liver injury revealed significant hepatocyte injury in livers perfused with the control defatting cocktail but no evidence of injury in livers perfused with either GDNF or vehicle. In vitro, GDNF reduced TG accumulation in HepG2 cells and stimulated increased TG lipolysis. In conclusion, GDNF can decrease mice liver fat content to an acceptable range and could be a potential defatting agent before liver transplantation. Liver Transplantation 22 459‐467 2016 AASLD