| First Author | Yu HM | Year | 2021 |
| Journal | Biochem Biophys Res Commun | Volume | 558 |
| Pages | 57-63 | PubMed ID | 33895552 |
| Mgi Jnum | J:305582 | Mgi Id | MGI:6706035 |
| Doi | 10.1016/j.bbrc.2021.04.038 | Citation | Yu HM, et al. (2021) The PDE5 inhibitor udenafil ameliorates nonalcoholic fatty liver disease by improving mitochondrial function. Biochem Biophys Res Commun 558:57-63 |
| abstractText | Nonalcoholic fatty liver disease (NAFLD) refers to a series of diseases, including simple steatosis, caused by the excessive accumulation of fat in hepatocytes, nonalcoholic steatohepatitis with inflammation and fibrosis, and more advanced forms of cirrhosis. The pathogenic mechanisms underlying fatty liver and the progression from simple fatty liver to hepatitis and cirrhosis remain unclear. One potentially unifying mechanism may be a dysregulation of free fatty acid oxidation. The oversupply of fatty acids to the liver can result in mitochondrial dysfunction leading to the accumulation of lipids in the liver. Interestingly, there have been several reports showing that inhibitors of phosphodiesterase 5 (PDE5) can increase mitochondrial biogenesis, preserve mitochondrial function in vitro. And, we have recently demonstrated that the phosphodiesterase type 5 inhibitor udenafil improves insulin sensitivity by increasing mitochondrial function in adipocytes. In this study, we aimed to examine the effects of the PDE5 inhibitor udenafil on NAFLD in the ob/ob mouse model. Treatment of ob/ob mice for 6 weeks with udenafil reduced fat mass and fasting glucose. Importantly, udenafil caused a reduction in lipid accumulation in the liver of these mice, including hepatic triglyceride (TG) and cholesterol levels. Mechanistically, udenafil decreased the proinflammatory cytokines in the liver. Also, udenafil increased the levels in the liver of the important lipolytic enzymes and the levels of several mitochondrial beta-oxidation related genes. Similar effects were seen in udenafil treated primary hepatocytes. We believe that our study makes a significant contribution to the literature because the results from our study suggest that udenafil may be an effective treatment for NAFLD by improving mitochondrial function. |
