Abstract
Objective
Recent evidence indicates that levels of breast milk (BM) hormones such as leptin can fluctuate with maternal adiposity, suggesting that BM hormones may signal maternal metabolic and nutritional environments to offspring during postnatal development. The hormone apelin is highly abundant in BM but its regulation during lactation is completely unknown. Here, we evaluated whether maternal obesity and overnutrition impacted BM apelin and leptin levels in clinical cohorts and lactating rats.
Methods
BM and plasma samples were collected from normal-weight and obese breastfeeding women, and from lactating rats fed a control or a high fat (HF) diet during lactation. Apelin and leptin levels were assayed by ELISA. Mammary gland (MG) apelin expression and its cellular localization in lactating rats was measured by quantitative RT-PCR and immunofluorescence, respectively.
Results
BM apelin levels increased with maternal BMI, whereas plasma apelin levels decreased. BM apelin was also positively correlated with maternal insulin and C-peptide levels. In rats, maternal HF feeding exclusively during lactation was sufficient to increase BM apelin levels and decrease its plasma concentration without changing body weight. In contrast, BM leptin levels increased with maternal BMI in humans, but did not change with maternal HF feeding during lactation in rats. Apelin is highly expressed in the rat MG during lactation and was mainly localized to mammary myoepithelial cells. We found that MG apelin gene expression was up-regulated by maternal HF diet and positively correlated with BM apelin content and maternal insulinemia.
Conclusions
Our study indicates that BM apelin levels increase with long- and short-term overnutrition, possibly via maternal hyperinsulinemia and transcriptional upregulation of MG apelin expression in myoepithelial cells. Apelin regulates many physiological processes, including energy metabolism, digestive function, and development. Further studies are needed to unravel the consequences of such changes in offspring development.
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Acknowledgements
We thank Valérie Montel, Anne Dickes and Phexmar animal housing facility for excellent help and support in animal studies; Elodie Richard at BICeL facility for microscopy and Barbara Deracinois for advice in MG peptides extractions.
Funding
This study was supported by grants of the French Ministry of Higher Education and Research, Lille University (BQR 2014), the FHU 1000 days for health (APELMILK project), the CHRU Lille hospital (OBAPE project) and Conseil Régional des Hauts-de-France. L.M. was supported by fellowships from Metropole Européenne Lilloise (MEL) and Conseil Régional des Hauts-de-France.
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Marousez, L., Hanssens, S., Butruille, L. et al. Breast milk apelin level increases with maternal obesity and high-fat feeding during lactation. Int J Obes 45, 1052–1060 (2021). https://doi.org/10.1038/s41366-021-00772-y
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DOI: https://doi.org/10.1038/s41366-021-00772-y
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