p53 as a double-edged sword in the progression of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) derives from the accumulation of hepatic lipids, which leads to liver steatosis and then triggers non-alcoholic steatohepatitis, sometimes worsening to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Although the molecular mechanisms of NAFLD have been intensively investigated, its pathogenesis remains poorly understood and needs to be clarified. Tumor-suppressor factor p53 has a crucial role in many signaling pathways that induce apoptosis and has become an emerging focus for liver disease research. Recent studies have revealed that p53 is linked to the development of NAFLD and that the regulation of p53 has therapeutic potential. However, the association between p53 and NAFLD remains controversial. Several reports have suggested that activated p53 plays an essential role in the pathogenesis of NAFLD, whereas others have indicated that suppression of p53 activation aggravates liver steatosis. Here, we review the relevant evidence suggesting that these two contrasting processes indicate a dual role of p53 in NAFLD progression and propose that the extent of NAFLD may be key to explaining the contradictory findings. In this review, the crosstalk among p53, lipid metabolism, insulin resistance, inflammation and oxidative stress in NAFLD is discussed, and we suggest that a better understanding of p53 would present a promising potential new strategy for NAFLD prevention and treatment.