Abnormal metabolic processes involved in the pathogenesis of non-alcoholic fatty liver disease (Review)

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and can lead to liver cirrhosis or liver cancer in severe cases. In recent years, the incidence of NAFLD has increased substantially. The trend has continued to increase and has become a key point of concern for health systems. NAFLD is often associated with metabolic abnormalities caused by increased visceral obesity, including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, atherosclerosis and systemic microinflammation. Therefore, the pathophysiological mechanisms of NAFLD must be clarified to develop new drug treatment strategies. Recently, researchers have conducted numerous studies on the pathogenesis of NAFLD and have identified various important regulatory factors and potential molecular mechanisms, providing new targets and a theoretical basis for the treatment of NAFLD. However, the pathogenesis of NAFLD is extremely complex and involves the interrelationship and influence of multiple organs and systems. Therefore, the condition must be explored further. In the present review, the abnormal metabolic process, including glucose, lipid, amino acid, bile acid and iron metabolism are reviewed. It was concluded that NAFLD is associated with an imbalanced metabolic network that involves glucose, lipids, amino acids, bile acids and iron, and lipid metabolism is the core metabolic process. The current study aimed to provide evidence and hypotheses for research and clinical treatment of NAFLD.

Keywords: lipid; mechanism; metabolism; non-alcoholic fatty liver disease; pathogenesis.

Figure 1

The metabolic network of NAFLD. NAFLD, non-alcoholic fatty liver disease; GLP-1, glucagon-like peptide 1; IR, insulin resistance; LOXL2, lysyl oxidase-like 2; FXR, farnesoid X receptor; LXRs, liver X receptors; PNPLA3, patatin-like phospholipase domain protein 3; BCAAs, branched chain amino acids; NPC1L1, Niemann-Pick c1-like 1; ROS, reactive oxygen species; (+), positive regulation; (-), negative regulation.