Lipidomic identification of urinary extracellular vesicles for non-alcoholic steatohepatitis diagnosis

Abstract

Background and Aims Non-alcoholic fatty liver disease (NAFLD) is a usual chronic liver disease and lacks non-invasive biomarkers for the clinical diagnosis and prognosis. Extracellular vesicles (EVs), a group of heterogeneous small membrane-bound vesicles, carry proteins and nucleic acids as promising biomarkers for clinical applications, but it has not been well explored on their lipid compositions related to NAFLD studies. Here, we investigate the lipid molecular function of urinary EVs and their potential as biomarkers for non-alcoholic steatohepatitis (NASH) detection. Methods This work includes 43 patients with non-alcoholic fatty liver (NAFL) and 40 patients with NASH. The EVs of urine were isolated and purified using the EXODUS method. The EV lipidomics was performed by LC-MS/MS. We then systematically compare the EV lipidomic profiles of NAFL and NASH patients and reveal the lipid signatures of NASH with the assistance of machine learning. Results By lipidomic profiling of urinary EVs, we identify 422 lipids mainly including sterol lipids, fatty acyl lipids, glycerides, glycerophospholipids, and sphingolipids. Via the machine learning and random forest modeling, we obtain a biomarker panel composed of 4 lipid molecules including FFA (18:0), LPC (22:6/0:0), FFA (18:1), and PI (16:0/18:1), that can distinguish NASH with an AUC of 92.3%. These lipid molecules are closely associated with the occurrence and development of NASH. Conclusion The lack of non-invasive means for diagnosing NASH causes increasing morbidity. We investigate the NAFLD biomarkers from the insights of urinary EVs, and systematically compare the EV lipidomic profiles of NAFL and NASH, which holds the promise to expand the current knowledge of disease pathogenesis and evaluate their role as non-invasive biomarkers for NASH diagnosis and progression.

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

“…Due to the elevated risk of mortality with these diseases, there is a need for strategies in its identification, prevention, and treatment within healthcare. In 2022, as evidenced in Figure 5, the bulk of research articles focussed on related diseases: CVD, 232–255 diabetes, 166,233,249,250,256–278 liver disease, 51,279–293 MetS 277,294,295 and obesity 277,295–305 …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 according to separation techniques, detectors, and RPLC columns used …”

“…,51,[279][280][281][282][283][284][285][286][287][288][289][290][291][292][293] MetS277,294,295 and obesity 277,[295][296][297][298][299][300][301][302][303][304][305]. Coleman et al investigated the pathogenesis and involvement of the gastrointestinal tract with the syndrome through multiple experiments including an untargeted RPLC-MS/MS analysis of faecal samples of people with MetS and healthy controls.…”

Lipidomics analysis reveals new insights into the goose fatty liver formation

“…Lipidomics, as a widely used analytical technique to analyze lipid metabolism, is helpful to search for NAFLD-related biomarkers ( Vvedenskaya et al, 2021 ). Numerous liver diseases have been found to cause changes in plasma lyso-phosphatidylcholines ( LPC ) levels, making LPC a potential biomarker for NAFLD ( Akerele and Cheema, 2015 ; Zhu et al, 2022 ). The ratio of phosphatidylcholines ( PC ) to phosphatidylethanolamines ( PE ) is a determinant of cell membrane integrity and a predictor of NAFLD ( Li et al, 2006 ).…”

Diabetes with kidney injury may change the abundance and cargo of urinary extracellular vesicles

“…Extracellular vesicles (EVs) are secreted by cells of all tissues and organs under normal and disease conditions, ranging in size from approximately 30 to 10,000 nm in diameter and containing surface receptors, membrane and soluble proteins, lipids, ribonucleic acids, and genomic and mitochondrial DNAs (5)(6)(7). Urinary extracellular vesicles (uEVs) are derived from epithelia throughout the urogenital tract, podocyte, and transitional epithelia from the urinary collection system and released into the urinary lumen.…”