Fibrinogen production is enhanced in an in-vitro model of non-alcoholic fatty liver disease: an isolated risk factor for cardiovascular events?. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Yeung, Emily; Treskes, Philipp; Martin, Sarah; Manning, Jonathan; Dunbar, Donald; Rogers, Sophie; Le Bihan, Thierry; Lockman, K.; Morley, Steven; Hayes, Peter; Nelson, Leonard; Plevris, John
• Is Part Of: Lipids in health and disease. Volume 14:Issue 1(2015)
• Page Start: 1
• Page End: 8
• Publication Date: 2015-12
• Subjects: Systems biology -- Proteomics -- Microarray -- STRING -- Non-alcoholic fatty liver disease -- Cardiovascular disease -- Metabolic syndrome -- C3A cells; Lipids -- Periodicals; Lipids in human nutrition -- Periodicals; Lipids -- Metabolism -- Disorders -- Periodicals; 616.3997
• DOI: 10.1186/s12944-015-0069-3
• Languages: English
• ISSNs: 1476-511X

Abstract

Abstract Background Cardiovascular disease (CVD) remains the major cause of excess mortality in patients with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the individual contribution of NAFLD to CVD risk factors in the absence of pathogenic influences from other comorbidities often found in NAFLD patients, by using an establishedin-vitro model of hepatic steatosis. Methods Histopathological events in non-alcoholic fatty liver disease were recapitulated by focused metabolic nutrient overload of hepatoblastoma C3A cells, using oleate-treated-cells and untreated controls for comparison. Microarray and proteomic data from cell culture experiments were integrated into a custom-built systems biology database and proteogenomics analysis performed. Candidate genes with significant dysregulation and concomitant changes in protein abundance were identified and STRING association and enrichment analysis performed to identify putative pathogenic pathways. Results The search strategy yielded 3 candidate genes that were specifically and significantly up-regulated in nutrient-overloaded cells compared to untreated controls: fibrinogen alpha chain (2.2 fold), fibrinogen beta chain (2.3 fold) and fibrinogen gamma chain (2.1 fold) (all rank products pfp <0.05). Fibrinogen alpha and gamma chain also demonstrated significant concomitant increases in protein abundance (3.8-fold and 2.0-fold, respectively, p <0.05). Conclusions In-vitro modelling of NAFLD and reactive oxygen species formation in nutrient overloaded C3A cells, in the absence of pathogenic influences from other comorbidities, suggests that NAFLD is an isolated determinant of CVD. Nutrient overload-induced up-regulation of all three fibrinogen component subunits of the coagulation cascade provides a possible mechanism to explain the excess CVD mortality observed in NAFLD patients.