Author information
1University of Cambridge, Department of Biochemistry, Cambridge, CB2 1GA, United Kingdom; Roger Williams Institute of Hepatology, Foundation for Liver Research, London, SE5 9NT, United Kingdom.
2Addenbrooke's Hospital, Cambridge Biomedical Research Centre, Department of Medicine, United Kingdom.
3Wellcome Trust-MRC Institute of Metabolic Science Metabolic Research Laboratories, Cambridge, CB2 0QQ, United Kingdom.
4Addenbrooke's Hospital, Cambridge Biomedical Research Centre, Department of Medicine, United Kingdom; Wellcome Trust-MRC Institute of Metabolic Science Metabolic Research Laboratories, Cambridge, CB2 0QQ, United Kingdom.
5Department of Biochemistry and Molecular and Cellular Biology, Veterinary Faculty, University of Zaragoza, Zaragoza, 50013, Spain.
6Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, SW7 2AZ, United Kingdom.
7University of Cambridge, Department of Biochemistry, Cambridge, CB2 1GA, United Kingdom.
8Faculty of Health and Life Sciences, Clinical and Biomedical Sciences, University of Exeter Medical School, RILD Building, Barrack Road, Exeter, EX2 5DW, United Kingdom.
9Wellcome Trust-MRC Institute of Metabolic Science Metabolic Research Laboratories, Cambridge, CB2 0QQ, United Kingdom. Electronic address: ak675@medschl.cam.ac.uk.
10University of Cambridge, Department of Biochemistry, Cambridge, CB2 1GA, United Kingdom; The Rowett Institute, Foresterhill Campus, University of Aberdeen, Aberdeen, AB25 2ZD, United Kingdom. Electronic address: jules.griffin@abdn.ac.uk.
11University of Cambridge, Department of Biochemistry, Cambridge, CB2 1GA, United Kingdom; Roger Williams Institute of Hepatology, Foundation for Liver Research, London, SE5 9NT, United Kingdom; Wellcome Trust-MRC Institute of Metabolic Science Metabolic Research Laboratories, Cambridge, CB2 0QQ, United Kingdom; Aldo Moro University of Bari, Department of Interdisciplinary Medicine, Clinica Medica "C. Frugoni", Bari, 70124, Italy. Electronic address: michele.vacca@uniba.it.
Abstract
Background and objectives: Non-alcoholic fatty liver disease (NAFLD) develops due to impaired hepatic lipid fluxes and is a risk factor for chronic liver disease and atherosclerosis. Lipidomic studies consistently reported characteristic hepatic/VLDL "lipid signatures" in NAFLD; whole plasma traits are more debated. Surprisingly, the HDL lipid composition by mass spectrometry has not been characterised across the NAFLD spectrum, despite HDL being a possible source of hepatic lipids delivered from peripheral tissues alongside free fatty acids (FFA). This study characterises the HDL lipidomic signature in NAFLD, and its correlation with metabolic and liver disease markers.
Methods: We used liquid chromatography-mass spectrometry to determine the whole serum and HDL lipidomic profile in 89 biopsy-proven NAFLD patients and 20 sex and age-matched controls.
Results: In the whole serum of NAFLD versus controls, we report a depletion in polyunsaturated (PUFA) phospholipids (PL) and FFA; with PUFA PL being also lower in HDL, and negatively correlated with BMI, insulin resistance, triglycerides, and hepatocyte ballooning. In the HDL of the NAFLD group we also describe higher saturated ceramides, which positively correlate with insulin resistance and transaminases.
Conclusion: NAFLD features lower serum lipid species containing polyunsaturated fatty acids; the most affected lipid fractions are FFA and (HDL) phospholipids; our data suggest a possible defect in the transfer of PUFA from peripheral tissues to the liver in NAFLD. Mechanistic studies are required to explore the biological implications of our findings addressing if HDL composition can influence liver metabolism and damage, thus contributing to NAFLD pathophysiology.