Multi-omic profiles of human nonalcoholic fatty liver disease tissue highlight heterogenic phenotypes

Non-alcoholic fatty liver disease (NAFLD) is a consequence of sedentary life style and high fat diets with an estimated prevalence of about 30% in western countries. It is associated with insulin resistance, obesity, glucose intolerance and drug toxicity. Additionally, polymorphisms in, e.g. APOC3, PNPLA3, NCAN and PPP1R3B, correlate with NAFLD. Several studies have already investigated later stages of the disease. This study characterizes and stratifies distinct grades of the early steatosis stages of the disease with the aim of identifying mechanisms underlying the etiology of the disease. We analyzed liver biopsies and serum samples from patients with distinct grades of steatosis (also pre-disease states) employing transcriptomics, serum biomarkers, metabolomics, and proteomics. We unveiled distinct transcriptome, proteome and metabolome profiles in patients with high-grade and low-grade steatosis. In line with previously reported causes of steatosis and insulin resistance our observed expression differences in the levels of cytokines, in the IGF-axis, in fat metabolism and branched chain amino acids provide a comprehensive image of the deregulated biological system underlying the disease.