Maternal and Postnatal High Linoleic Acid Diet Impacts Lipid Metabolism in Adult Rat Offspring in a Sex-Specific Manner

Abstract

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. We aimed to investigate the effect of maternal and postnatal high LA (HLA) diet on plasma FA composition, plasma and hepatic lipids and genes involved in lipid metabolism in the liver of adult offspring. Female rats were fed with low LA (LLA; 1.44% LA) or HLA (6.21% LA) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), fed either LLA or HLA diets and sacrificed at PN180. Postnatal HLA diet decreased circulating total n-3 PUFA and alpha-linolenic acid (ALA), while increased total n-6 PUFA, LA and arachidonic acid (AA) in both male and female offspring. Maternal HLA diet increased circulating leptin in female offspring, but not in males. Maternal HLA diet decreased circulating adiponectin in males. Postnatal HLA diet significantly decreased aspartate transaminase (AST) in females and downregulated total cholesterol, HDL-cholesterol and triglycerides in the plasma of males. Maternal HLA diet downregulated the hepatic mRNA expression of Hmgcr in both male and female offspring and decreased the hepatic mRNA expression of Cpt1a and Acox1 in females. Both maternal and postnatal HLA diet decreased hepatic mRNA expression of Cyp27a1 in females. Postnatal diet significantly altered circulating fatty acid concentrations, with sex-specific differences in genes that control lipid metabolism in the adult offspring following exposure to high LA diet in utero.

Importance of Windows of Exposure to Maternal High-Fat Diet and Feto-Placental Effects: Discrimination Between Pre-conception and Gestational Periods in a Rabbit Model

“…In rats, in the context of high-fat diet (HFD), high consumption of LA during pregnancy was reported to affect liver FA profiles of offspring in a similar manner, with increased ω6 PUFA and decreased MUFA ( Marchix et al, 2020a ). Surprisingly, however, and as previously observed in rabbits ( Tarrade et al, 2013 ) and rats ( Shrestha et al, 2021 ) fed with a high-fat diet rich in LA, FA concentrations in liver neutral lipids were similar among groups.…”

Camellia (Camellia oleifera Abel.) Seed Oil Regulating of Metabolic Phenotype and Alleviates Dyslipidemia in High Fat-Fed Mice through Serum Branch-Chain Amino Acids

“…Pantothenate and CoA biosynthesis are strongly involved in the metabolism of the fatty acids, and a UPLC-MS-based urine nontargeted metabolic profiling implied that pantothenate and coenzyme A biosynthesis pathway alteration was the most prominent in diabetic kidney disease (a major prevalent chronic microvascular complication of type 2 diabetes) subjects [33]. Linoleic acid is competent in CO and has been widely proved to be linked with liver lipid accumulation [34,35]. Additionally, the current study indicated that linoleic acid metabolism is also involved in serum lipid levels.…”

Sex-Specific Differences in Lysine, 3-Hydroxybutyric Acid and Acetic Acid in Offspring Exposed to Maternal and Postnatal High Linoleic Acid Diet, Independent of Diet

“…In our previous study, we reported that maternal and postnatal diet high in LA alters metabolic parameters, mainly circulating leptin and cholesterol, in adult offspring in a sex-specific manner [ 15 ]. In this study, there is no alteration in measured metabolites among the dietary groups, so that maternal and postnatal LA had no effect on the distribution of metabolites in the adult offspring.…”

“…However, there are limited data studying the effect of high LA diet during pregnancy on offspring health. Recently, we have demonstrated that high maternal LA affects offspring cardiac function [14] and metabolic parameters [15] in a rat model.…”