Regulation of UCP2 in nonalcoholic fatty liver disease: From mechanisms to natural product

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with lipid deposition in liver cells and/or subsequent inflammation, excluding other known causes. NAFLD is a subset of metabolic syndrome that ranges from simple steatohepatitis (NASH), fibrosis to cirrhosis and hepatocellular carcinoma (HCC). At present, the pathogenesis of NAFLD remains unclear. Among the many factors that shape these transitions, uncoupling protein 2 (UCP2) may be involved in every stage of the disease. UCP2 is a carrier protein that responds to fatty acids (FAs) in mitochondrial intima and has a wide tissue distribution. However, the biological function of UCP2 has not been fully elucidated, and most of our current knowledge comes from cell and animal experiments. These data suggest that UCP2 plays a role in lipid metabolism, oxidative stress, apoptosis, and even cancer. In this review, we summarize the structure, distribution, and biological function of UCP2 and its role in the progression of NAFLD, as well as natural products targeting UCP2 to improve NAFLD.