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

Abstract

Background: Linoleic acid (LA) is an essential polyunsaturated fatty acid (PUFA) that is required for foetal growth and development. Excess intake of LA can be detrimental for metabolic health due to its pro-inflammatory properties; however, the effect of a diet high in LA on offspring metabolites is unknown. In this study, we aimed to determine the role of maternal or postnatal high linoleic acid (HLA) diet on plasma metabolites in adult offspring. Methods: Female Wistar Kyoto (WKY) rats were fed with either low LA (LLA) or HLA diet for 10 weeks prior to conception and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), treated with either LLA or HLA diets and sacrificed at PN180. Metabolite analysis was performed in plasma samples using Nuclear Magnetic Resonance. Results: Maternal and postnatal HLA diet did not alter plasma metabolites in male and female adult offspring. There was no specific clustering among different treatment groups as demonstrated by principal component analysis. Interestingly, there was clustering among male and female offspring independent of maternal and postnatal dietary intervention. Lysine was higher in female offspring, while 3-hydroxybutyric acid and acetic acid were significantly higher in male offspring. Conclusion: In summary, maternal or postnatal HLA diet did not alter the plasma metabolites in the adult rat offspring; however, differences in metabolites between male and female offspring occurred independently of dietary intervention.

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

“…Developmental programming of disease risk due to an adverse maternal environment during pregnancy has led to the identification of sex-specific effects on offspring outcomes [8][9][10][11][12][13]. To add to this field of study, we have investigated the effects of a maternal HLA diet on rodent offspring lipid metabolism, and circulating lipids and fatty acids in adult offspring [12].…”

Maternal Diet High in Linoleic Acid Alters Renal Branching Morphogenesis and mTOR/AKT Signalling Genes in Rat Fetal Kidneys

“…Developmental programming of disease risk due to an imbalanced maternal diet during pregnancy has led to the identification of sex-specific effects in offspring outcomes [11,[22][23][24][25][26]. Therefore, in this study, we aimed to investigate the effects of a maternal high-LA (HLA) diet on targets responsible for renal development in embryonic rat offspring.…”

“…Therefore, in this study, we aimed to investigate the effects of a maternal high-LA (HLA) diet on targets responsible for renal development in embryonic rat offspring. As developmental programming is often sex-specific [11,[22][23][24][25][26], we analysed both male and female embryonic offspring independently. It was hypothesised that the kidneys of offspring from mothers consuming an HLA diet would have altered branching morphogenesis, angiogenesis and leptin and megalin signalling compared to those from offspring of mothers consuming an LLA diet, with males being more significantly affected than females.…”

Early Life Nutrition and the Development of Offspring Metabolic Health

“…In the two manuscripts from Shrestha et al, the effects of a maternal high omega 6 (linoleic acid) diet during pregnancy and in the weaning/postnatal period were investigated in the adolescent [ 7 ] and adult [ 8 ] offspring. In adolescence, analysis of the metabolome identified changes in both sexes that were independent of the diet.…”

“…In adolescence, analysis of the metabolome identified changes in both sexes that were independent of the diet. In the female offspring, lysine concentrations were higher, while 3-hydroxybutyric acid and acetic acid were significantly higher in the male offspring [ 7 ]. In the adult offspring exposed to an elevated maternal and postnatal linoleic acid diet, postnatal linoleic acid decreased circulating omega 3 fatty acids and increased circulating omega 6 fatty acids in both sexes.…”