Associations between long-chain PUFAs in maternal blood, cord blood, and breast milk and offspring body composition up to 5 years: follow-up from the INFAT study

Meyer, Dorothy; Brei, Christina; Stecher, Lynne; Much, Daniela; Brunner, Stefanie; Hauner, Hans

doi:10.1038/s41430-018-0388-3

Cited by 9 publications

(23 citation statements)

References 29 publications

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“…For convenience, the clinical characteristics for mothers and their offspring of the n-3 LCPUFA intervention group (N3, n = 21; female n = 10, male = 11) and control group (Con, n = 20; female n = 11, male = 9) as already described in our previous report [10] are shown in Additional file 1: Table S1 in the present report. The characteristics of the INFAT study subpopulation largely resemble the data of the whole INFAT study population (n = 208) which demonstrated that the n-3 LCPUFA intervention effectively reduced the n-6/n-3 LCPUFA ratio as expected [12,34]. In addition, no adverse effects for mothers or offspring were observed in the study population.…”

Section: Resultsmentioning

confidence: 64%

“…We recently reported on several analyses of the INFAT population (n = 208) that explored adipose tissue development in relation to fetal programming and offspring obesity risk [7,10,[31][32][33][34], including a report on sex-specific placental gene regulation and function in a defined INFAT subpopulation of mother-offspring pairs (n = 41) [10]. The present secondary analysis took advantage of the mRNA, microRNA, and protein samples derived from the same placental specimens of the aforementioned INFAT subpopulation [10] and offered a unique opportunity to explore the impact of maternal n-3 LCPUFA supplementation on placental microRNA, mRNA, and protein expression, and potential microRNA-mRNA interactions and downstream targets.…”

Section: Introductionmentioning

confidence: 99%

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Fetal sex modulates placental microRNA expression, potential microRNA-mRNA interactions, and levels of amino acid transporter expression and substrates: INFAT study subpopulation analysis of n-3 LCPUFA intervention during pregnancy and associations with offspring body composition

Sedlmeier

Meyer

Stecher

et al. 2021

BMC Mol and Cell Biol

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Background Previously, we revealed sexually dimorphic mRNA expression and responsiveness to maternal dietary supplementation with n-3 long-chain polyunsaturated fatty acids (LCPUFA) in placentas from a defined INFAT study subpopulation. Here, we extended these analyses and explored the respective placental microRNA expression, putative microRNA-mRNA interactions, and downstream target processes as well as their associations with INFAT offspring body composition. Results We performed explorative placental microRNA profiling, predicted microRNA-mRNA interactions by bioinformatics, validated placental target microRNAs and their putative targets by RT-qPCR and western blotting, and measured amino acid levels in maternal and offspring cord blood plasma and placenta. microRNA, mRNA, protein, and amino acid levels were associated with each other and with offspring body composition from birth to 5 years of age. Forty-six differentially regulated microRNAs were found. Validations identified differential expression for microRNA-99a (miR-99a) and its predicted target genes mTOR, SLC7A5, encoding L-type amino acid transporter 1 (LAT1), and SLC6A6, encoding taurine transporter (TauT), and their prevailing significant sexually dimorphic regulation. Target mRNA levels were mostly higher in placentas from control male than from female offspring, whereas respective n-3 LCPUFA responsive target upregulation was predominantly found in female placentas, explaining the rather balanced expression levels between the sexes present only in the intervention group. LAT1 and TauT substrates tryptophan and taurine, respectively, were significantly altered in both maternal plasma at 32 weeks’ gestation and cord plasma following intervention, but not in the placenta. Several significant associations were observed for miR-99a, mTOR mRNA, SLC7A5 mRNA, and taurine and tryptophan in maternal and cord plasma with offspring body composition at birth, 1 year, 3 and 5 years of age. Conclusions Our data suggest that the analyzed targets may be part of a sexually dimorphic molecular regulatory network in the placenta, possibly modulating gene expression per se and/or counteracting n-3 LCPUFA responsive changes, and thereby stabilizing respective placental and fetal amino acid levels. Our data propose placental miR-99, SLC7A5 mRNA, and taurine and tryptophan levels in maternal and fetal plasma as potentially predictive biomarkers for offspring body composition.

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Section: Resultsmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Fetal sex modulates placental microRNA expression, potential microRNA-mRNA interactions, and levels of amino acid transporter expression and substrates: INFAT study subpopulation analysis of n-3 LCPUFA intervention during pregnancy and associations with offspring body composition

Sedlmeier

Meyer

Stecher

et al. 2021

BMC Mol and Cell Biol

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“…The long-term follow-up afforded us the opportunity to observe that several relationships between perinatal determinants and offspring body composition change over time. For example, while significant associations between n-3 and n-6 LCPUFAs, leptin, and adiponectin in maternal blood, cord blood, and breast milk were present early in life (19,28,30), they did not persist up to 5 years (20,29,31,32), as summarized in Table 1. This is an important observation to consider in planning future longitudinal studies, as around 5 years is known as the age of adiposity rebound and is thought to be a critical age that can predict later obesity (33).…”

Section: Lessons Learned From the Infat Study: Implications For Practicementioning

confidence: 99%

“…In this manuscript, we will focus primarily on the objectives of the initial and follow-up studies, which are the key findings in the first two publications in Table 1 under the heading Body Composition in Newborns, Infants, and Children . However, we also made use of our extensive data set by pooling the intervention and control groups to explore relationships between perinatal dietary macronutrient and fatty acid exposure and offspring body composition ( 18 – 20 , 23 ). These results are summarized in Table 1 .…”

Section: Lessons Learned From the Infat Study: Implications For Practmentioning

confidence: 99%

Evaluation of Maternal Dietary n-3 LCPUFA Supplementation as a Primary Strategy to Reduce Offspring Obesity: Lessons From the INFAT Trial and Implications for Future Research

et al. 2020

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Preclinical research suggests that early exposure to LCPUFAs is associated with offspring health outcomes, although evidence in humans is rather unclear. In 2006, we established the Impact of Nutritional Fatty acids during pregnancy and lactation on early human Adipose Tissue development (INFAT) study, a prospective randomized controlled intervention trial that examined whether decreasing the n-6/n-3 LCPUFA ratio during pregnancy and lactation influences offspring adipose tissue development in children up to 5 years. Our results indicate that maternal supplementation with n-3 LCPUFAs does not reduce offspring obesity risk, which is in line with recent publications. This perspective describes the challenges and lessons learned from our clinical trial. We discuss key findings and critically evaluate differences in study design, methodology, and analyses across similar intervention trials that may partly explain heterogeneous results. Summarizing evidence from human trials, we conclude that n-3 LCPUFA supplementation should not be recommended as a primordial strategy to prevent childhood obesity. Instead, it remains unknown whether n-3 LCPUFA supplementation could benefit high-risk subgroups and some vulnerable maternal/child populations. The perspectives offered herein are derived largely from insights gained from ours and similar n-3 LCPUFA intervention trials and help to provide direction for future research that examines the impact of maternal nutritional exposure on offspring health and disease outcomes.

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“…Whilst there appears to be more robust data supporting the beneficial effects of omega-3 fatty acids on mature adipocytes [11][12][13], their biological effects on developing adipose tissue are far less clear. Evidence suggesting beneficial or detrimental effects of the two families of PUFA in the maternal diet on offspring growth and adiposity, have largely been based on in vitro studies or animal experiments and recent data have suggested limited reproduction of these results in human trials [53]. Further studies are required to investigate the effects of maternal dietary PUFA on developing tissues but caution should be exercised in the meantime not to extrapolate from data on mature tissues and to highlight the detrimental effects of a maternal high-fat intake regardless of the types of fats consumed.…”

Section: Discussionmentioning

confidence: 99%

Omega-6:Omega-3 Fatty Acid Ratio and Total Fat Content of the Maternal Diet Alter Offspring Growth and Fat Deposition in the Rat

et al. 2020

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Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) have been shown to inhibit lipogenesis and adipogenesis in adult rats. Their possible early life effects on offspring fat deposition, however, remain to be established. To investigate this, female Wistar rats (n = 6–9 per group) were fed either a 9:1 ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) or a lower 1:1.5 ratio during pregnancy and lactation. Each ratio was fed at two total fat levels (18% vs. 36% fat w/w) and offspring were weaned onto standard laboratory chow. Offspring exposed to a 36% fat diet, irrespective of maternal dietary LA:ALA ratio, were lighter (male, 27 g lighter; female 19 g lighter; p < 0.0001) than those exposed to an 18% fat diet between 3 and 8 weeks of age. Offspring exposed to a low LA (18% fat) diet had higher proportions of circulating omega-3 LCPUFA and increased gonadal fat mass at 4 weeks of age (p < 0.05). Reduced Srebf1 mRNA expression of hepatic (p < 0.01), gonadal fat (p < 0.05) and retroperitoneal fat (p < 0.05) tissue was observed at 4 weeks of age in male and female offspring exposed to a 36% fat diet, and hepatic Srebf1 mRNA was also reduced in male offspring at 8 weeks of age (p < 0.05). Thus, while offspring fat deposition appeared to be sensitive to both maternal dietary LA:ALA ratio and total fat content, offspring growth and lipogenic capacity of tissues appeared to be more sensitive to maternal dietary fat content.

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Associations between long-chain PUFAs in maternal blood, cord blood, and breast milk and offspring body composition up to 5 years: follow-up from the INFAT study

Cited by 9 publications

References 29 publications

Fetal sex modulates placental microRNA expression, potential microRNA-mRNA interactions, and levels of amino acid transporter expression and substrates: INFAT study subpopulation analysis of n-3 LCPUFA intervention during pregnancy and associations with offspring body composition

Fetal sex modulates placental microRNA expression, potential microRNA-mRNA interactions, and levels of amino acid transporter expression and substrates: INFAT study subpopulation analysis of n-3 LCPUFA intervention during pregnancy and associations with offspring body composition

Evaluation of Maternal Dietary n-3 LCPUFA Supplementation as a Primary Strategy to Reduce Offspring Obesity: Lessons From the INFAT Trial and Implications for Future Research

Omega-6:Omega-3 Fatty Acid Ratio and Total Fat Content of the Maternal Diet Alter Offspring Growth and Fat Deposition in the Rat

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