ACC-1 as a Possible Biochemical Indicator of Lipoapoptosis in In Vivo and In Vitro Models of MAFLD.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is an emerging condition with a worldwide prevalence ranging from 6% to 35% and is very frequent among patients with obesity, diabetes, or metabolic syndrome. One of the main challenges in the treatment of this disease is the identification of a reliable and direct biomarker to diagnose the stage of hepatic steatosis before it progresses to steatohepatitis. This is especially important as many patients remain asymptomatic until cirrhosis develops. The aim of this study was to analyze the expression of the enzyme acetyl-CoA carboxylase 1 (ACC-1) in vitro in a model of lipocytotoxicity using HepG2 cells as well as in vivo in Wistar rats. Our results demonstrate an accumulation of lipid inclusions in hepatocytes observed both in vitro and in experimental models of hepatic steatosis, leading to membrane damage. This allows for the detection of ACC-1 enzyme in the extracellular medium at short induction times, in contrast to the appearance of AST and ALT, which become detectable only once the damage becomes more invasive. ACC-1 could potentially serve as a clinical indicator to detect fatty liver disease before it progresses to steatohepatitis and fibrosis, allowing for timely and non-invasive treatment for patients.