Abstract
Objective
The lactation-suckling period is critical for white adipose tissue (WAT) development. Early postnatal nutrition influences later obesity risk but underlying mechanisms remain elusive. Here, we tested whether altered postnatal nutrition specifically during suckling impacts epigenetic regulation of key metabolic genes in WAT and alter long-term adiposity set point.
Methods
We analyzed the effects of maternal high-fat (HF) feeding in rats exclusively during lactation-suckling on breast milk composition and its impact on male offspring visceral epidydimal (eWAT) and subcutaneous inguinal (iWAT) depots during suckling and in adulthood.
Results
Maternal HF feeding during lactation had no effect on mothersâ body weight (BW) or global breast milk composition, but induced qualitative changes in breast milk fatty acid (FA) composition (high n-6/n-3 polyunsaturated FA ratio and low medium-chain FA content). During suckling, HF neonates showed increased BW and mass of both eWAT and iWAT depot but only eWAT displayed an enhanced adipogenic transcriptional signature. In adulthood, HF offspring were predisposed to weight gain and showed increased hyperplastic growth only in eWAT. This specific eWAT expansion was associated with increased expression and activity of stearoyl-CoA desaturase-1 (SCD1), a key enzyme of FA metabolism. SCD1 converts saturated FAs, e.g. palmitate and stearate, to monounsaturated FAs, palmitoleate and oleate, which are the predominant substrates for triglyceride synthesis. Scd1 upregulation in eWAT was associated with reduced DNA methylation in Scd1 promoter surrounding a PPARγ-binding region. Conversely, changes in SCD1 levels and methylation were not observed in iWAT, coherent with a depot-specific programming.
Conclusions
Our data reveal that maternal HF feeding during suckling programs long-term eWAT expansion in part by SCD1 epigenetic reprogramming. This programming events occurred with drastic changes in breast milk FA composition, suggesting that dietary FAs are key metabolic programming factors in the early postnatal period.
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Acknowledgements
The authors thank Valérie Montel, Anne Dickes-Coopman, and Phexmar animal housing facility for excellent technical support, BICeL facility for microscopy, and Joel Haas for critical review of the manuscript. This study was supported by grants of the French Ministry of Higher Education and Research, of Lille University (BQR 2014) and from the French âHeart and Arteriesâ Foundation. Laura Butruille and Lucie Marousez were supported by grants from Metropole Européenne Lilloise (MEL) and Conseil Régional des Hauts-de-France.
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Butruille, L., Marousez, L., Pourpe, C. et al. Maternal high-fat diet during suckling programs visceral adiposity and epigenetic regulation of adipose tissue stearoyl-CoA desaturase-1 in offspring. Int J Obes 43, 2381â2393 (2019). https://doi.org/10.1038/s41366-018-0310-z
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DOI: https://doi.org/10.1038/s41366-018-0310-z
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