These authors contributed equally to the study.
Fat-Derived Hormone Adiponectin Combined with FTY720 Significantly Improves Small-for-Size Fatty Liver Graft Survival
Article first published online: 10 FEB 2006
American Journal of Transplantation
Volume 6, Issue 3, pages 467–476, March 2006
How to Cite
Man, K., Zhao, Y., Xu, A., Lo, C.M., Lam, K.S.L., Ng, K.T., Ho, J.W.Y., Sun, C.K., Lee, T.K., Li, X.L. and Fan, S.T. (2006), Fat-Derived Hormone Adiponectin Combined with FTY720 Significantly Improves Small-for-Size Fatty Liver Graft Survival. American Journal of Transplantation, 6: 467–476. doi: 10.1111/j.1600-6143.2005.01201.x
- Issue published online: 10 FEB 2006
- Article first published online: 10 FEB 2006
- Received 05 September 2005, revised 25 October 2005 and accepted for publication 31 October 2005.
- cell survival signaling;
- hepatic microcirculation;
- liver transplantation;
- marginal graft
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.