Interactive effects of maternal and weaning high linoleic acid intake on hepatic lipid metabolism, oxylipins profile and hepatic steatosis in offspring

Abstract : Non-alcoholic fatty liver disease (NAFLD) has been described as a hepatic manifestation of the metabolic syndrome. When several studies correlated maternal linoleic acid (LA) intake with the development of obesity, only few links have been made between n-6 fatty acid (FA) and NAFLD. Herein, we investigated the influence of both maternal and weaning high LA intake on lipid metabolism and susceptibility to develop later metabolic diseases in offspring. Pregnant rats were fed a control-diet (2% LA) or a LA-rich diet (l2% LA) during gestation and lactation. At weaning, offspring was assigned to one of the two diets, i.e. either maintained on the same maternal diet or fed the other diet for six months. Physiological, biochemical parameters and hepatic FA metabolism were analyzed. We demonstrated that the interaction between the maternal and weaning LA intake altered metabolism in offspring and could lead to hepatic steatosis. This phenotype was associated with altered hepatic FA content and lipid metabolism. Interaction between maternal and weaning LA intake led to a specific pattern of n-6 and n-3 oxylipins that could participate to the development of hepatic steatosis in offspring. Our findings highlight the significant interaction between maternal and weaning high LA intake to predispose offspring to later metabolic disease and support the predictive adaptive response hypothesis.