University of Cambridge, Department of Biochemistry, Cambridge, CB2 1GA, United Kingdom; Roger Williams Institute of Hepatology, Foundation for Liver Research, London, SE5 9NT, United Kingdom.
Addenbrooke's Hospital, Cambridge Biomedical Research Centre, Department of Medicine, United Kingdom.
Mol Metab. 2023 Jul;73:101728. doi: 10.1016/j.molmet.2023.101728. Epub 2023 Apr 19.
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.
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.
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.
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.
非酒精性脂肪性肝病（NAFLD）是由于肝内脂质流紊乱引起的，是慢性肝病和动脉粥样硬化的危险因素。脂质组学研究一致报告了 NAFLD 中特征性的肝脏/VLDL“脂质特征”；全血浆特征则更具争议性。令人惊讶的是，尽管 HDL 可能是与游离脂肪酸（FFA）一起从外周组织输送到肝脏的脂质的来源，但 NAFLD 谱中尚未通过质谱法对 HDL 的脂质组成进行特征描述。本研究旨在描述 NAFLD 中 HDL 的脂质组学特征及其与代谢和肝病标志物的相关性。
我们使用液相色谱-质谱法测定了 89 例经活检证实的 NAFLD 患者和 20 名性别和年龄匹配的对照者的全血清和 HDL 脂质组学特征。
在 NAFLD 与对照组的全血清中，我们报告多不饱和（PUFA）磷脂（PL）和 FFA 减少；HDL 中的 PUFA PL 也较低，与 BMI、胰岛素抵抗、甘油三酯和肝细胞气球样变呈负相关。在 NAFLD 组的 HDL 中，我们还描述了较高的饱和神经酰胺，其与胰岛素抵抗和转氨酶呈正相关。
NAFLD 的特征是血清中含有多不饱和脂肪酸的脂质种类减少；受影响最大的脂质组分为 FFA 和（HDL）磷脂；我们的数据表明，NAFLD 中可能存在外周组织向肝脏输送 PUFA 的缺陷。需要进行机制研究来探索我们的发现的生物学意义，以确定 HDL 组成是否会影响肝脏代谢和损伤，从而有助于 NAFLD 的病理生理学。
