The consequences of n-3 polyunsaturated fatty acids (PUFA) depletion on hepatic lipid metabolism in mice

In the present study, we investigated the consequences of n-3 polyunsaturated fatty acids (PUFA) depletion on hepatic lipid metabolism in mice fed during three months with a diet presenting a high n-6/n-3 PUFA ratio to induce n-3 PUFA depletion. Microarray analyses were performed to identify the molecular targets involved in the development of hepatic steatosis associated with n-3 PUFA depletion. Male C57Bl/6J mice (9 weeks old) were housed in groups of four mice per cage at 22°C in a 12h light/dark cycle and given free access to diet and water. After an acclimatization period of 1 week, the mice were fed a control (CT) or an n-3 PUFA-depleted diet (DEF) for 3 months. At the end of the study period, mice (CT, n=6; DEF, n=7) were anesthetized after a 6h period of fasting. Some mice (CT: n=4 et DEF: n=7) were anesthetized without being starved. A fraction of the main liver lobe was fixed-frozen in isopentane and kept at -80°C for histological analysis. The excess tissue material was immediately clamped in liquid N2 and kept at -80°C. All mice experiments were approved by the local animal ethics committee, and the housing conditions were as specified by the Belgian Law of November 14, 1993 on the protection of laboratory animals (agreement n° LA 1230314).