Non-Alcoholic Fatty Liver Disease (NAFLD): Molecular Mechanism, Pathological Progression and Treatment

Abstract

Non-alcoholic fatty liver disease (NAFLD), currently is considered the most common liver disease in the world, affects up to a quarter of the people. NAFLD, characterized by hepatic steatosis, is associated with numerous adverse outcomes and high mortality. Furthermore, fatty acid uptake and de novo lipogenesis production outstrips fatty acid oxidation and export, leading to hepatic steatosis. Hepatic fatty acid uptake beside de novo lipogenesis are enhanced in NAFLD, whereas compensatory fatty acid oxidation is inadequate to normalize lipid levels and, by inducing oxidative stress, may contribute to cellular damage and disease progression, especially when the function of mitochondrial is impaired and increased peroxisomal and cytochromal oxidation. Although lipid output initially increases, it levels off and may decrease as the disease progresses, thereby promoting fat gain. NAFLD is closely associated with many current lifestyle-related diseases, as hepatic steatosis can lead to systemic metabolic imbalances affecting multiple organs. This overview focuses on four major pathways that promote hepatic lipid homeostasis while we discuss the molecular causes of NAFLD