In the present study, we created a new Syrian golden hamster model lacking Apoa5 gene using CRISPR/Cas9 gene editing to demonstrate that loss of endogenous ApoA5 caused HTG and hepatic steatosis under chow diet condition and HFD aggravated the development of NAFLD through regulating circadian gene Nr1d1, providing a new molecular mechanism by which ApoA5 protested against NAFLD; however, these metabolic phenotypes has no or minor effects on atherogenesis on different dietary interventions, respectively. The gene discussed is APOA5; the disease is fatty liver disease.