Maternal and postnatal diet high in linoleic acid alters fatty acid composition, cholesterol and hepatic gene expression, in adult offspring in a sex-specific manner

Abstract

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. The consumption of LA has increased over the last decades due to availability in foods. In this study, we aimed to investigate the effect of maternal and postnatal diet high in LA (HLA) diet on plasma fatty acid (FA) composition, plasma and hepatic lipids, and genes involved in lipid metabolism in the liver of adult offspring, and any benefit of postnatal diet low in LA. Female rats were fed with low LA (LLA; 1.44% energy from LA: recommended daily intake) or HLA (6.21% energy from LA: what Australians are consuming) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), fed LLA or HLA diets and sacrificed at PN180 (6 months old). Postnatal HLA diet increased the brain weight as a percentage of body weight in adult male offspring. Postnatal HLA diet decreased circulating total n-3 PUFA and alpha-linolenic acid (ALA), while increased circulating total n-6 PUFA, LA and arachidonic acid (AA) in both male and female offspring. There were no differences in fat mass, systolic blood pressure, glucose tolerance and insulin sensitivity among the groups. Maternal HLA diet increased circulating leptin in female offspring, but not in male offspring. Interestingly, maternal HLA diet decreased adiponectin concentration in the plasma of male offspring, but not in females. Postnatal HLA diet significantly decreased aspartate transaminase (AST), a circulating liver enzyme, in female offspring, however, other liver enzymes such as alanine transaminase (ALT) and alkaline phosphatase (ALP) remained unchanged. Furthermore, postnatal HLA diet downregulated total cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride in the plasma of male offspring, but not in females. There were no differences in hepatic cholesterol and triglycerides among the groups. Interestingly, maternal HLA diet downregulated the mRNA expression of Hmgcr (3-hydroxy-3- methyl-glutaryl-coenzyme A reductase) in the liver of both male and female offspring. Maternal HLA diet decreased the mRNA expression of Cpt1a and Acox1 in the liver of female offspring. In conclusion, maternal and postnatal HLA diet affected the plasma FA composition, circulating adiponectin, leptin and lipids, and hepatic expression of genes related to lipid metabolism in the adult offspring in a sex-specific manner. This may contribute the altered lipid metabolism in the liver and development of lipid dysfunction associated with chronic conditions like non-alcoholic fatty liver disease in the adult offspring.