Copper Deficiency Promotes Lipid Toxicity In the Liver

Background: Metabolic-associated fatty liver disease (MAFLD) is a condition characterized by fat accumulation in the liver and progression of liver damage to inflammation, fibrosis, and liver failure. Previous studies have suggested that copper deficiency is linked to the pathogenesis of MAFLD. Copper is an essential cofactor for enzymes, including superoxide dismutase (SOD1), cytochrome c oxidase (CCO), and ceruloplasmin (Cp). Therefore, copper deficiency may impair mitochondrial ATP generation, increase oxidative stress, and dysregulate iron transport, contributing to liver steatosis and dysfunction. Hypothesis: A high-fat diet (HFD) may dysregulate copper uptake and utilization to impair copper-dependent enzyme expression and activities, exacerbating the onset and progression of MAFLD. Objective: This research will determine the effects of HFD and surplus fatty acids on mice and cultured hepatocytes on copper-containing enzymes' expression levels and activities. Results: The data show that excess fatty acids significantly change copper-dependent enzyme expression levels and activities. Significance and impacts: Future studies on the relationship between metabolic stress of excess fat and copper dysregulation can help better understand the mechanism behind MAFLD and advance the cure for MAFLD patients.