Metabolic and lipidomic profiling of steatotic human livers during ex situ normothermic machine perfusion guides resuscitation strategies


Autoři: Siavash Raigani aff001;  Negin Karimian aff002;  Viola Huang aff002;  Anna M. Zhang aff003;  Irene Beijert aff002;  Sharon Geerts aff002;  Sonal Nagpal aff002;  Ehab O. A. Hafiz aff005;  Fermin M. Fontan aff002;  Mohamed M. Aburawi aff002;  Paria Mahboub aff002;  James F. Markmann aff001;  Robert J. Porte aff004;  Korkut Uygun aff001;  Martin Yarmush aff001;  Heidi Yeh aff001
Působiště autorů: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America aff001;  Center for Engineering in Medicine, Massachusetts General Hospital and Shriners Hospital for Children, Boston, Massachusetts, United States of America aff002;  Tufts University School of Medicine, Boston, Massachusetts, United States of America aff003;  Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, Netherlands aff004;  Electron Microscopy Research Division, Theodor Bilharz Research Institute, Giza, Egypt aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0228011

Souhrn

There continues to be a significant shortage of donor livers for transplantation. One impediment is the discard rate of fatty, or steatotic, livers because of their poor post-transplant function. Steatotic livers are prone to significant ischemia-reperfusion injury (IRI) and data regarding how best to improve the quality of steatotic livers is lacking. Herein, we use normothermic (37°C) machine perfusion in combination with metabolic and lipidomic profiling to elucidate deficiencies in metabolic pathways in steatotic livers, and to inform strategies for improving their function. During perfusion, energy cofactors increased in steatotic livers to a similar extent as non-steatotic livers, but there were significant deficits in anti-oxidant capacity, efficient energy utilization, and lipid metabolism. Steatotic livers appeared to oxidize fatty acids at a higher rate but favored ketone body production rather than energy regeneration via the tricyclic acid cycle. As a result, lactate clearance was slower and transaminase levels were higher in steatotic livers. Lipidomic profiling revealed ω-3 polyunsaturated fatty acids increased in non-steatotic livers to a greater extent than in steatotic livers. The novel use of metabolic and lipidomic profiling during ex situ normothermic machine perfusion has the potential to guide the resuscitation and rehabilitation of steatotic livers for transplantation.

Klíčová slova:

Bile – Biopsy – Fatty acids – Fatty liver – Lipid metabolism – Lipid profiles – Liver – Liver transplantation


Zdroje

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