Maternal Diet High in Linoleic Acid Alters Offspring Lipids and Hepatic Regulators of Lipid Metabolism in an Adolescent Rat Model

Abstract

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. A maternal high LA (HLA) diet alters cardiovascular development in adolescent rats and hepatic function in adult rats in a sex-specific manner. We investigated the effects of an HLA diet on adolescent offspring hepatic lipids and hepatic lipid metabolism gene expression, and the ability of the postnatal diet to alter these effects. Female Wistar Kyoto rats were fed low LA (LLA; 1.44% energy from LA) or high LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring, weaned at postnatal day (PN) 25, were fed LLA or HLA and euthanised at PN40 (n = 6-8). Maternal HLA increased circulating uric acid, decreased hepatic cholesterol and increased hepatic Pparg in males, whereas only hepatic Srebf1 and Hmgcr increased in females. Postnatal (post-weaning) HLA decreased liver weight (% body weight) and increased hepatic Hmgcr in males, and decreased hepatic triglycerides in females. Maternal and postnatal HLA had an interaction effect on Lpl, Cpt1a and Pparg in females. These findings suggest that an HLA diet both during and after pregnancy should be avoided to improve offspring disease risk.

Keywords: linoleic acid; maternal; offspring; sex-specific liver.

Figure 1

Effect of maternal or postnatal diet high in linoleic acid on cholesterol and triglyceride contents in the liver of adolescent offspring. (A,B) liver cholesterol (C,D) liver triglycerides, (A,C) male and (B,D) female. Data are presented as mean ± standard error of the mean (SEM). Two-way ANOVA was performed for statistical analysis with maternal diet and postnatal diet as two factors. n = 6–8. LLA: low linoleic acid; HLA: high linoleic acid. ns: non-significant.

Figure 2

Effect of maternal or postnatal diet high in linoleic acid on expression of genes related to lipid metabolism. (A,B) Lpl, (C,D) Srebf1, (E,F) Ldlr, (G,H) Hmgcr. (A,C,E,G) are for males and (B,D,F,H) are for females. Data are presented as mean ± standard error of the mean (SEM). Two-way ANOVA was performed for statistical analysis with maternal diet and postnatal diet as two factors. n = 6–8. LLA: low linoleic acid; HLA: high linoleic acid. Where post hoc analysis identified a difference, differences across the groups are denoted by an asterix (* p < 0.05). ns: non-significant.

Figure 3

Effect of maternal or postnatal diet high in linoleic acid on expression of genes related to fatty acid oxidation. (A,B) Cyp27a1, (C,D) Acox1, (E,F) Pparg. (A,C,E) are for males and (B,D,F) are for females. Data are presented as mean ± standard error of the mean (SEM). Two-way ANOVA was performed for statistical analysis with maternal diet and postnatal diet as two factors. n = 6–8. LLA: low linoleic acid; HLA: high linoleic acid. ns: non-significant.