This work presents the first application of high-resolution magic angle spinning (HR-MAS) 1H NMR spectroscopy to human liver biopsy samples, allowing a determination of their metabolic profiles before removal from donors, during cold perfusion, and after implantation into recipients. The assignment of peaks observed in the 1H HR-MAS NMR spectra was aided by the use of two-dimensional J-resolved, TOCSY and 1H-13C
HMQC spectra. The spectra were dominated by resonances from
triglycerides,
phospholipids, and
glycogen and from a variety of small molecules including glycerophosphocholine (GPC),
glucose,
lactate,
creatine,
acetate,
amino acids, and
nucleoside-related compounds such as
uridine and
adenosine. In agreement with histological data obtained on the same biopsies, two of the six livers were found to contain high amounts of
triglycerides by NMR spectroscopy, which also indicated that these tissues contained a higher degree of unsaturated
lipids and a lower proportion of
phospholipids and low molecular weight compounds. Additionally,
proton T2 relaxation times indicated two populations of
lipids, a higher mobility
triglyceride fraction and a lower mobility
phospholipid fraction, the proportions of which changed according to the degree of fat content. GPC was found to decrease from the pretransplant to the posttransplant biopsy of all livers except for one with a histologically confirmed high
lipid content, and this might represent a
biomarker of liver function posttransplantation. NMR signals produced by the liver preservation
solution were clearly detected in the cold perfusion stage biopsies of all livers but remained in the posttransplant spectra of only the two livers with a high
lipid content and were prominent mainly in the graft that later developed
primary graft dysfunction. This study has shown biochemical differences between livers used for transplants that can be related to the degree and type of
lipid composition. This technology might therefore provide a novel screening approach for donor organ quality and a means to assess function in the recipient after
transplantation.