We found that supaglutide treatment reduced the weight of liver. The reduced liver mass was associated with decreased hepatocyte fat deposition and TG content. Remarkably, supaglutide-reduced liver fat accumulation was also accompanied by decreased ALT and AST levels, suggesting enhanced hepatic protective capability from HFD induced liver injury. It has been shown that excessive lipid accumulation within hepatocytes is the main cause to hepatocyte injury characterized by increased ALT and AST concentrations (Magee et al., 2016). Previous studies showed that HFD induced hepatic lipid accumulation was associated with increased liver inflammation, elevated hepatic endoplasmic reticulum stress and activation relevant signaling pathways (Liu et al., 2014), in which the obese-related liver injury could be ameliorated by GLP-1 treatment or therapies using GLP-1 mimetic (Armstrong et al., 2016a,b; Bouchi et al., 2016; He et al., 2016; Valdecantos et al., 2016).