Gene therapy using AAV8-mediated NR1D1 overexpression or ApoA5 restoration significantly attenuated hepatic steatosis in ApoA5-/- hamsters with or without affecting plasma lipid profiling, respectively, whereas activation of adipose tissue by exposure to cold or CL316243 completely ameliorated hyperlipidemia and hepatic steatosis due to ApoA5 deficiency. This evidence concerns the gene APOA5 and fatty liver disease.