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.
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Amersi, F
Farmer, DG
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Farmer, DG
Shaw, GD
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Shaw, GD
Kato, H
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Kato, H
Coito, AJ
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Coito, AJ
Kaldas, F
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Kaldas, F
Zhao, DL
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Zhao, DL
Lassman, CR
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Lassman, CR
Melinek, J
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Melinek, J
Ma, J
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Ma, J
Volk, HD
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Volk, HD
Kupiec-Weglinski, JW
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h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Kupiec-Weglinski, JW
Busuttil, RW
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h-index: 0
机构:
Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Chui, AKK
Shi, LW
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Shi, LW
Rao, ARN
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Rao, ARN
Verran, DJ
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h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Verran, DJ
Painter, D
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h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Painter, D
Koorey, D
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h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Koorey, D
McCaughan, GW
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
McCaughan, GW
Sheil, AGR
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Amersi, F
Farmer, DG
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Farmer, DG
Shaw, GD
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Shaw, GD
Kato, H
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Kato, H
Coito, AJ
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Coito, AJ
Kaldas, F
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Kaldas, F
Zhao, DL
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Zhao, DL
Lassman, CR
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Lassman, CR
Melinek, J
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Melinek, J
Ma, J
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Ma, J
Volk, HD
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Volk, HD
Kupiec-Weglinski, JW
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
Kupiec-Weglinski, JW
Busuttil, RW
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Sch Med, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat,Dept Surg, Los Angeles, CA 90095 USA
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Chui, AKK
Shi, LW
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Shi, LW
Rao, ARN
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Rao, ARN
Verran, DJ
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Verran, DJ
Painter, D
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Painter, D
Koorey, D
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
Koorey, D
McCaughan, GW
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia
McCaughan, GW
Sheil, AGR
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, AustraliaUniv Sydney, Australian Natl Liver Transplant Unit, Royal Prince Alfred Hosp, Camperdown, NSW, Australia