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

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22062946 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2946

Author(s):

Nirajan Shrestha ◽

Josif Vidimce ◽

Olivia J. Holland ◽

James S. M. Cuffe ◽

Belinda R. Beck ◽

...

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Linoleic Acid ◽

Mrna Expression ◽

Female Offspring ◽

Female Rats ◽

Adult Offspring ◽

Total N ◽

High Linoleic Acid ◽

Male And Female

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.

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FADS1 rs174550 genotype and high linoleic acid diet modify plasma PUFA phospholipids in a dietary intervention study

European Journal of Nutrition ◽

10.1007/s00394-021-02722-w ◽

2021 ◽

Author(s):

Topi Meuronen ◽

Maria A. Lankinen ◽

Olli Kärkkäinen ◽

Markku Laakso ◽

Jussi Pihlajamäki ◽

...

Keyword(s):

Linoleic Acid ◽

Multiple Testing ◽

Dietary Intervention ◽

Daily Intake ◽

Phospholipid Composition ◽

Plasma Phospholipid ◽

Plasma Metabolites ◽

High Linoleic Acid ◽

Fasting Plasma ◽

Long Chain

Abstract Introduction Fatty acid desaturase 1 (FADS1) gene encodes for delta-5 desaturase enzyme which is needed in conversion of linoleic acid (LA) to arachidonic acid (AA). Recent studies have shown that response to dietary PUFAs differs between the genotypes in circulating fatty acids. However, interactions between the FADS1 genotype and dietary LA on overall metabolism have not been studied. Objectives We aimed to examine the interactions of FADS1 rs174550 genotypes (TT and CC) and high-LA diet to identify plasma metabolites that respond differentially to dietary LA according to the FADS1 genotype. Methods A total of 59 men (TT n = 26, CC n = 33) consumed a sunflower oil supplemented diet for 4 weeks. Daily dose of 30, 40, or 50 ml was calculated based on body mass index. It resulted in 17–28 g of LA on top of the usual daily intake. Fasting plasma samples at the beginning and at the end of the intervention were analyzed with LC–MS/MS non-targeted metabolomics method. Results At the baseline, the carriers of FADS1 rs174550-TT genotype had higher abundance of long-chain PUFA phospholipids compared to the FADS1 rs174550-CC one. In response to the high-LA diet, LA phospholipids and long-chain acylcarnitines increased and lysophospholipids decreased in fasting plasma similarly in both genotypes. LysoPE (20:4), LysoPC (20:4), and PC (16:0_20:4) decreased and cortisol increased in the carriers of rs174550-CC genotype; however, these genotype–diet interactions were not significant after correction for multiple testing. Conclusion Our findings show that both FADS1 rs174550 genotype and high-LA diet modify plasma phospholipid composition. Trial registration The study was registered to ClinicalTrials: NCT02543216, September 7, 2015 (retrospectively registered).

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Chronic consumption of a high linoleic acid diet during pregnancy, lactation and post-weaning period increases depression-like behavior in male, but not female offspring

Behavioural Brain Research ◽

10.1016/j.bbr.2021.113538 ◽

2021 ◽

pp. 113538

Author(s):

Suk-yu Yau ◽

Yvette Siu Ling Yip ◽

Douglas Formolo ◽

Siyuen He ◽

Thomas Ho Yin Lee ◽

...

Keyword(s):

Linoleic Acid ◽

Female Offspring ◽

High Linoleic Acid ◽

Acid Diet ◽

Linoleic Acid Diet

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Maternal diet high in linoleic acid alters offspring fatty acids and cardiovascular function in a rat model

British Journal Of Nutrition ◽

10.1017/s0007114521001276 ◽

2021 ◽

pp. 1-37

Author(s):

Nirajan Shrestha ◽

Simone L Sleep ◽

Tessa J Helman ◽

Olivia J Holland ◽

James SM Cuffe ◽

...

Keyword(s):

Fatty Acids ◽

Linoleic Acid ◽

Cardiac Function ◽

Maternal Diet ◽

Cardiovascular Function ◽

Hdl Cholesterol ◽

Female Offspring ◽

Total Plasma ◽

Alpha Linolenic Acid ◽

Wistar Kyoto

Abstract Linoleic acid (LA), an essential n-6 fatty acid (FA), is critical for fetal growth and development. We investigated the effects of maternal high LA (HLA) diet on offspring cardiac development and how it relates to circulating FAs and cardiovascular function in adolescent offspring, and the ability of the postnatal diet to reverse any adverse effects. Female Wistar Kyoto rats were fed low LA (LLA; 1.44% energy from LA) or HLA (6.21% energy from LA) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring, weaned at postnatal day 25 (PN25), were fed LLA or HLA diets and euthanised at PN40 (n = 6-8). Maternal HLA diet decreased circulating total cholesterol and HDL-cholesterol in females and decreased total plasma n-3 FA in males, while maternal and postnatal HLA diets decreased total plasma n-3 FA in females. Alpha- linolenic acid (ALA) and eicosapentaenoic acid (EPA) were decreased by postnatal but not maternal HLA diets in both sexes. Maternal and postnatal HLA diets increased total plasma n-6 and LA, and a maternal HLA diet increased circulating leptin, in both male and female offspring. Maternal HLA decreased slopes of systolic and diastolic PVRs, and increased cardiac Col1a1, Col3a1, Atp2a1 and Notch1 in males. Maternal and postnatal HLA diets left-shifted the diastolic PVR in female offspring. Coronary reactivity was altered in females, with differential effects on flow repayment after 10–20 sec occlusions. In conclusion, maternal HLA diets impact lipids, fatty acids and cardiac function in offspring, with postnatal diet modifying fatty acids and cardiac function in the female offspring.

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Exercise during pregnancy mitigates negative effects of parental obesity on metabolic function in adult mouse offspring

Journal of Applied Physiology ◽

10.1152/japplphysiol.00641.2020 ◽

2020 ◽

Author(s):

Rhianna Che C. Laker ◽

Ali Altıntaş ◽

Travis S. Lillard ◽

Mei Zhang ◽

Jessica J. Connelly ◽

...

Keyword(s):

Skeletal Muscle ◽

Dna Methylation ◽

Female Offspring ◽

Adult Offspring ◽

Peroxisome Proliferator ◽

Negative Consequences ◽

Female Adult ◽

Peroxisome Proliferator Activated Receptor ◽

Male And Female ◽

Maternal Exercise

Parental health influences embryonic development and susceptibility to disease in the offspring. We investigated whether maternal voluntary running during gestation could protect the offspring from the adverse effects of maternal or paternal high-fat diet (HF) in mice. We performed transcriptomic and whole-genome DNA methylation analyses in female offspring skeletal muscle as well as targeted DNA methylation analysis of the peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α) promoter in the both male and female adult offspring. Maternal HF resulted in impaired metabolic homeostasis in male offspring at 9 months of age, while both male and female offspring were negatively impacted by paternal HF. Maternal exercise during gestation completely mitigated these metabolic impairments. Female adult offspring from obese male or female parent had skeletal muscle transcriptional profiles enriched in genes regulating inflammation and immune responses, whereas maternal exercise resulted in a transcriptional profile similar to offspring from normal chow fed parents. Maternal HF, but not paternal HF, resulted in hypermethylation of the Pgc-1α promoter at CpG -260, which was abolished by maternal exercise. These findings demonstrate the negative consequences of maternal and paternal HF for the offspring's metabolic outcomes later in life possibly through different epigenetic mechanisms, and maternal exercise during gestation mitigates the negative consequences.

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Placental treatment improves cardiac tolerance to ischemia/reperfusion insult in adult male and female offspring exposed to prenatal hypoxia

Pharmacological Research ◽

10.1016/j.phrs.2021.105461 ◽

2021 ◽

Vol 165 ◽

pp. 105461

Author(s):

Nataliia Hula ◽

Floor Spaans ◽

Jennie Vu ◽

Anita Quon ◽

Raven Kirschenman ◽

...

Keyword(s):

Adult Male ◽

Ischemia Reperfusion ◽

Female Offspring ◽

Prenatal Hypoxia ◽

Male And Female

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Perinatal SSRIs, maternal stress, and their effects on social behaviors in male and female offspring

Toxicology Letters ◽

10.1016/j.toxlet.2017.07.185 ◽

2017 ◽

Vol 280 ◽

pp. S72

Author(s):

Jodi Pawluski

Keyword(s):

Maternal Stress ◽

Social Behaviors ◽

Female Offspring ◽

Male And Female

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PRE-MATERNAL ISOLATION EFFECTS ON BEHAVIOUR AND ENDOCRINE FUNCTION OF OFFSPRING

Acta Endocrinologica ◽

10.1530/acta.0.0620367 ◽

1969 ◽

Vol 62 (2) ◽

pp. 367-384 ◽

Cited By ~ 2

Author(s):

A. M. Sackler ◽

A. S. Weltman ◽

R. Schwartz ◽

P. Steinglass

Keyword(s):

Locomotor Activity ◽

Growth Rates ◽

Female Offspring ◽

The Body ◽

Endocrine Function ◽

Male And Female ◽

Isolation Stress ◽

Developmental Growth ◽

Body Weights ◽

And Control

ABSTRACT This report was designed to determine combined effects of maternal endocrine imbalances and abnormal behaviour due to prolonged isolation stress of female mice on the behaviour, developmental growth rate and endocrine function of their offspring. Sixty female albino mice averaging 19 g were divided equally into isolated and control groups. The isolated females were housed singly; control females were maintained in groups of 2 mice per cage. After observation of behavioural and physiological effects characteristic of isolation stress in the test mice, all isolated and control mice were mated after a 6½ month experimental, isolation period. No differences were observed in fertility and fecundity of the two groups of mothers. Analyses of developmental growth rates of the litters of the isolated versus control mothers showed significantly lower body weights in the test offspring at 3 and 4 weeks of age. The body weights of the female offspring remained significantly lower from the 4th to 11th weeks. The effects on the body weights of the male offspring declined and were no longer statistically significant at the 5th to 11 weeks. Locomotor activity at 4½ and 8 weeks of age was markedly or significantly higher in the male and female mice from isolated mothers. Tail-blood samples taken prior to autopsy at 5 and 11 weeks of age revealed significant decreases in the total leukocyte and eosinophil counts of both sexes. At the two ages, the absolute and relative spleen and thymus weights of the male and female offspring were markedly and/or significantly lower than the values observed in counterpart young from control females. Significant decreases were also observed in the absolute gonadal organ weights of both sexes at 11 weeks of age. The various data indicated inhibited growth rates, heightened locomotor activity and evasiveness, as well as evidence of increased adrenocortical function in the offspring from test mothers. The gonadal weight decreases suggested retarded gonadal development. Further studies using split-litter techniques are required to differentiate the effects of prenatal endocrine imbalances versus postnatal maternal influence (i. e., nursing care) on the offspring.

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