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Lactosylceramide induced by elastin-derived peptides decreases adipocyte differentiation

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Abstract

Elastin, the major protein of the extracellular matrix, is specially found in cardiovascular tissues and contributing to 30–50% of the dry weight of blood vessels. Elastin regulates cell signalling pathways involved in morphogenesis, injury response and inflammation. The function of elastin is frequently compromised in damaged or aged elastic tissues. Indeed, elastin degradation, observed during ageing, and the resulting production of elastin-derived peptides (EDPs), have crucial impacts on cardiovascular disease (atherosclerosis, thrombosis) or on metabolism disease progressions (type 2 diabetes or non-alcoholic steatohepatitis). In the present study, we analysed the EDP effects on 3T3 preadipocyte cell differentiation. In a first part, we treated 3T3-L1 cells with EDP and visualized the lipid droplet accumulation by the oil red O staining and measured the expression of various transcription factors and adipocyte-specific mRNAs by real-time RT-PCR. We demonstrated that the elastin receptor complex, ERC, is activated by EDPs and decreased adipocyte differentiation by a modulation of crucial adipogenesis transcriptional factor particularly PPARγ. In a second part, we identified the signalling pathway implicated in EDP-reduced cell differentiation. The flow cytometry and immunocytochemistry approaches showed that ERC activated by EDP produced a second messenger, lactosylceramide (Lac-Cer). Moreover, this Lac-Cer production favoured the phosphorylation of ERK1–2 (p-ERK1–2), to decrease adipocyte differentiation by a modulation of adipogenesis transcriptional factor PPARγ. To conclude, the EDP/Lac-Cer/p-ERK1–2 signalling pathway may be studied further as a critical target for treating complications associated with adipocyte dedifferentiation such as obesity and diabetes insulin resistance.

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Acknowledgements

We thank Stephane Betoulle for her technical support with flow cytometry. This work was supported by the University of Reims Champagne-Ardenne and the Centre National de la Recherche Scientifique (CNRS).

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  1. Thinhinane Hocine, Sebastien Blaise, Beatrice Romier-Crouzet and Hassan El Btaouri contributed equally to this work.

Authors and Affiliations

  1. UMR CNRS 7369 MEDyC, SFR CAP-Sante, Université de Reims Champagne-Ardenne, Reims, France

    Thinhinane Hocine, Sebastien Blaise, Cathy Hachet, Alexandre Guillot, Herve Sartelet, Pascal Maurice, Amar Bennasroune, Laurent Martiny, Laurent Duca, Beatrice Romier-Crouzet & Hassan EL Btaouri

  2. UMR-CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), UFR Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, Moulin de la Housse, BP 1039, 51687, Reims cedex, France

    Hassan EL Btaouri

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KEY points

Elastin-derived peptides (EDPs) decreased PPARγ expression.

EDPs reduced adipocyte differentiation.

Adipocyte differentiation is reduced by Lac-cer production and ERK1/2 activation.

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Hocine, T., Blaise, S., Hachet, C. et al. Lactosylceramide induced by elastin-derived peptides decreases adipocyte differentiation. J Physiol Biochem 76, 457–467 (2020). https://doi.org/10.1007/s13105-020-00755-z

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