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Maternal high-fat diet during suckling programs visceral adiposity and epigenetic regulation of adipose tissue stearoyl-CoA desaturase-1 in offspring

International Journal of Obesity volume 43, pages 2381–2393 (2019)Cite this article

Subjects

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 mothers’ 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 “Heart and Arteries” 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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  1. These authors contributed equally: Laura Butruille, Lucie Marousez

Authors and Affiliations

  1. Univ. Lille, EA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F-59000, Lille, France

    Laura Butruille, Lucie Marousez, Charlène Pourpe, Frédérik Oger, Simon Lecoutre, Céline Guinez, Christine Laborie, Philippe Deruelle, Christophe Breton, Jean Lesage & Delphine Eberlé

  2. Laboratoire de Biochimie et Nutrition Humaine INRA 1378, Agrocampus Ouest, 65 rue de Saint Brieuc, 35042, Rennes cedex, France

    Daniel Catheline & Philippe Legrand

  3. Leibniz Institute for Farm Animal Biology (FBN), Institute of Nutritional Physiology, D-18196, Dummerstorf, Germany

    Solvig Görs & Cornelia C. Metges

  4. Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000, Lille, France

    Jérôme Eeckhoute

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  1. Laura Butruille
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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, 2381–2393 (2019). https://doi.org/10.1038/s41366-018-0310-z

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