Emerging novel targets for nonalcoholic fatty liver disease treatment: Evidence from recent basic studies

Abstract

Nonalcoholic fatty liver disease (NAFLD), a leading chronic disease worldwide, affects approximately a quarter of the global population. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD and is more likely to progress to liver fibrosis than simple steatosis. NASH is also identified as the most rapidly growing cause of hepatocellular carcinoma. Although in the past decade, several phase II/III clinical trials have shown promising results in the use of novel drugs targeting lipid synthase, farnesoid X receptor signaling, peroxisome proliferator-activated receptor signaling, hepatocellular injury, and inflammatory signaling, proven pharmaceutical agents to treat NASH are still lacking. Thus, continuous exploration of the mechanism underlying the pathogenesis of NAFLD and the identification of novel therapeutic targets remain urgent tasks in the field. In the current review, we summarize studies reported in recent years that not only provide new insights into the mechanisms of NAFLD development but also explore the possibility of treating NAFLD by targeting newly identified signaling pathways. We also discuss evidence focusing on the intrahepatic targets involved in the pathogenesis of NAFLD as well as extrahepatic targets affecting liver metabolism and function.

Butylphthalide protects against ischemia-reperfusion injury in rats via reducing neuron ferroptosis and oxidative stress

“…11 Heme oxygenase (HO) is the rate-limiting enzyme in the process of heme catabolism, which can catalyze the degradation of heme to carbon monoxide, biliverdin, and free iron. 12 The degradation products of heme have the characteristics of immune regulation, anti-apoptosis, and vasodilation. The release of free iron is conducive to the formation of ferritin heavy chain and the activation of membrane transporter Fe-ATPase, which can reduce the content of intracellular free iron by promoting intracellular iron efflux, thus reducing cell oxidative damage.…”