Fat-Derived Hormone Adiponectin Combined with FTY720 Significantly Improves Small-for-Size Fatty Liver Graft Survival |
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Authors: | K. Man Y. Zhao A. Xu C.M. Lo K.S.L. Lam K.T. Ng J.W.Y. Ho C.K. Sun T.K. Lee X.L. Li S.T. Fan |
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Affiliation: | Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China. kwanman@hkucc.hku.hk |
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Abstract: | Owing to the discrepancy between organ donation and the demand for liver transplantation, expanding the liver donor pool is of vital importance. However, marginal liver grafts, such as small-for-size and/or fatty grafts, were associated with primary graft nonfunction or poor function. Therefore, novel combination therapies to rescue small-for-size fatty liver grafts should be investigated. In this study, we applied a combination therapy using a fat-derived hormone adiponectin (anti-steatosis) plus immunomodulator FTY720 (anti-inflammatory) in a rat liver transplantation model using small-for-size fatty liver grafts, and investigated the underlying protective mechanism such as anti-steatosis, intra-graft energy metabolism, hepatic microcirculatory changes, cell signaling cascades for survival, apoptosis and inflammation. The current study demonstrated that even a single treatment of adiponectin or FTY720 improved the 7-day graft survival from 0% to 62.5% (p = 0.001). The combination therapy significantly increased the 7-day graft survival rate to 100% by remarkable attenuation of graft steatosis and acute phase inflammatory response, significant activation of cell survival Akt pathway and maintenance of intra-graft adenosine triphosphate metabolism and improvement of hepatic microcirculation. In conclusion, the fat-derived hormone adiponectin combined with FTY720 might be a novel combination drug therapy for prevention of small-for-size fatty liver graft injury. |
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Keywords: | Anti-steatosis cell survival signaling hepatic microcirculation liver transplantation marginal graft |
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