Development of a Chicken Model of Nonalcoholic Fatty Liver Disease Induced by High Cholesterol and Low Choline Diet

Abstract

Non‐alcoholic fatty liver disease (NAFLD), a most common liver disease in human, is one of the primary causes of the laying hen death in chicken farming. It leads to a great commercial loss in agricultural sector. Therefore, reliable chicken models of NAFLD is required for the research of NAFLD etiology and prevention in chickens. To generate rapid chicken models of NAFLD, 7‐week‐old ISA chickens were fed with control diet (18% dietary protein, 4.72% fat, and 1300 mg/kg choline), low protein and high fat diet (LPHF, 13% dietary protein, 8.95% fat, and 1300 mg/kg choline), high cholesterol with low choline diet (CLC, 18% dietary protein, 4.72% fat, 2% cholesterol, and 800 mg/kg choline), or low protein, high fat, low choline, and high cholesterol diet (LPHFCLC, 13% CP, 8.95% fat, 2% cholesterol, and 800 mg/kg choline) for 4 weeks. Compared with control group, CLC and LPHFCLC treatments significantly elevated the level of plasma triglyceride and cholesterol. The appearance and the histological sections of the livers showed that CLC and LPHFCLC treatments significantly led to the accumulation of fat in the livers. The symptoms of steatohepatitis, hepatic ballooning and immune infiltration, were presented in the livers in CLC and LPHFCLC groups. In addition, the levels of dipeptidyl‐peptidase 4, a biomarker of fatty liver hemorrhagic syndrome in laying hens, were also increased in the plasma of CLC and LPHFCLC treatments. These data indicated that the diet with 2% cholesterol and 800 mg/kg choline was sufficient to induce hepatic steatosis and steatohepatitis. Moreover, the genes related to lipogenesis (PPARG, SREBP1C, and FASN) and pro‐inflammation cytokines (TNFA and IL1B) were elevated in the CLC group, further confirming the effects of CLC treatment on laying hens. Interestingly, CLC treatment also induced non‐alcoholic fatty livers in Plymouth Rock broiler chickens. It suggested that CLC treatment may induce non‐alcoholic fatty liver disease in different strains of chickens. Therefore, our data suggested that CLC treatment may induced rapid and reliable non‐alcoholic fatty liver disease in chickens. Accordingly, de novo lipogenesis is primary occurred in the livers both in chicken and human. This model can be expected to be utilized for the screening of functional components to prevent or improve fatty livers in chickens and human.