Cyclo(His-Pro): A further step in the management of steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) is now considered to be the most common liver disease in the world, and despite this has no approved therapy. The naturally occurring compound Cyclo (His-Pro) (CHP) has been described as having anti-inflammatory and hypoglycemic properties. We show that CHP administration in a mouse model of NAFLD/NASH protects against disease progression. Based on our study, CHP prevents overall lipid accumulation, reducing body weight and fat mass. The treatment lowers systemic inflammation and prevents the development of insulin resistance. Specifically, the effect of CHP in the liver is remarkable, it reduces the steatosis while preventing inflammation and fibrosis, typical features of NADLF/NASH progression. The analysis of the liver transcriptome underscores the anti-fibrotic and anti-inflammatory effects of the treatment, supported by histology results. CHP, which has an excellent safety record, may hence represent a novel approach to manage NAFLD. We assessed the effectiveness of CHP on the evolution of NAFLD/NASH that was induced in male C57BL/6J mice by housing them at thermoneutrality (TN) and feeding a western diet (WD). Histological and molecular characterizations were performed to assess the validity of our NASH mouse model and the effect of CHP in the context of liver disease.