Non-alcoholic fatty liver disease (NAFLD) associated fibrosis is an unrecognised component of obesity-related dysregulation and is associated with cardiovascular disease, liver-related and overall mortality, particularly in bariatric surgical patients. Obese patients are at a greater risk of liver fibrosis but may respond to weight loss. We presently lack practical and specific means of screening, diagnosing, staging and monitoring progression of NAFLD-associated fibrosis.
To identify liver-secreted proteins from livers with NAFLD-mediated fibrosis compared to livers with no pathology (NP) in a bariatric population.
Bariatric surgical patients (N=96, 74% female) were recruited. Intra-operative large liver wedge biopsy and plasma were collected and grouped based on liver histology into NP N=26, NAFLD F0 N=21, NAFLD F1 N=23 and NAFLD F2-3 N=26. Livers were precision-cut at 300µm, cultured (16hrs) and secreted proteins were extracted and compared between groups using liquid chromatography and tandem mass spectrometry. Differences in protein abundance were determined by student’s t-test with false discovery ratio set at p<0.05.
Overall age and body mass index (BMI) of patients was 41.8±10.4 and 43.3±6.7, respectively. There was no difference in age (NP=42.2±13.2, NAFLD F0=39.7±8.8, NAFLD F1=38.9±7.8, NAFLD F2-3=45.7±9.8) or BMI (NP=41.9±6.1, NAFLD F0=42.3±6.6, NAFLD F1=45.5±7.4, NAFLD F2-3=43.7±6.4) between groups. A total of 2,588 liver-secreted proteins were detected in the proteomic analysis and 1844 proteins were secreted in all groups. Seven proteins were significantly altered in NAFLD F2-3 compared to livers with NP (p<0.05). One protein, Yasminogen was secreted from NAFLD F2-3 livers (3.4±0.6) to a greater extent compared to livers with NP (1.0±0.2), NAFLD F0 (0.7±0.2) NAFLD F1 (1.1±0.3) (p<0.0001). Yasminogen is detected in plasma.
We have characterised the NAFLD-mediated fibrosis secreted proteome and discovered Yasminogen as a potential biomarker for NAFLD-associated fibrosis. This may prove an important tool in stratifying patients and importantly, providing the capacity for routine monitoring of disease status.