Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patientdisease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) antiinflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production. Key words: Non-alcoholic fatty liver disease; Proteomics; Genomics; Metabolic syndrome; Pathophysiology Core tip: Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder in Western populations. NAFLD can occur as a spectrum diseases, from simple steatosis, to non-alcoholic steatohepatitis characterised by hepatocellular injury and inflammation, to cirrhosis and hepatocellular carcinoma. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. This review highlighted several functional proteins and genetic polymoprhisms; particular those involved in insulin resistance, triglycerides metabolism and hepatic inflammation. It is hoped that this review will offer further insights into the pathophysiology of NAFLD.

Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries

“…Towards this goal, a pathology-supported genetic testing approach could prove useful in developing standardized pre-screen diagnostic algorithms to select non-responders to standard therapies and genetically uncharacterized NAFLD patients set to derive additional benefit from extended whole genome or exome sequencing [191,192] . Next-generation sequencing could be used to validate common susceptibility variants implicated in the etiopathogenesis of NAFLD, thereby supporting the development and validation of a genomics-based screening panel to provide greater insight into the value of personalized medicine applications [193,194] . In this context, a transdisciplinary "omics" approach has been proposed as a means of developing novel prognostic signatures incorporating relevant biochemical and genomic markers to optimize clinical diagnosis and improve risk management in patients with NAFLD [195] .…”

Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis

“…For these reasons, the circulatory levels of this protein have been considered a target in the diagnosis and treatment of CVD, as well as diabetes and obesity [38]. Moreover, different proteomic studies [39] have shown that a deficiency of plasmatic apolipoproteins is associated with a higher prevalence of NAFLD. This is in concordance with our findings, since the abundance of apolipoprotein A-IV was lower in urine samples from the H groups (fold change −2.20 in HA and −1.72 in HL, Table 2) compared to group N, reflecting the fact that this apolipoprotein is mainly present in HDL lipoproteins, whose plasma levels were reduced in these groups.…”

Matrix Metalloproteinases and Their Tissue Inhibitors in Patients with Nonalcoholic Fatty Liver Disease

“…The various calculated prognostic formula for assessment of fibrosis severity are suggested for clinical practice, such as APRI, ELF, NAFLD Fibrosis Score, FIB-4, FibroFast, FibroIndex, FibroMeter, FPI, Forns, GUCI, Hepascore, HALT-C, MDA, PGA, PGAA; however, the sensitivity and specificity of each formula are different and are not determined [15]. In particular, the information about MMP-9 and TIMP-1 & 2 as the direct markers in pathogenesis, diagnosis and prognosis for liver fibrosis in NAFLD is limited and controversy [16,17].…”