Lactosylceramide induced by elastin-derived peptides decreases adipocyte differentiation.

Fiche publication


Date publication

juin 2020

Journal

Journal of physiology and biochemistry

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BLAISE Sébastien, Dr DUCA Laurent, Pr MARTINY Laurent, Dr EL BTAOURI Hassan, Dr BENNASROUNE Amar


Tous les auteurs :
Hocine T, Blaise S, Hachet C, Guillot A, Sartelet H, Maurice P, Bennasroune A, Martiny L, Duca L, Romier-Crouzet B, El Btaouri H

Résumé

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.

Mots clés

Adipocyte, Differentiation, ERK, Elastin-derived peptides, Lactosylceramide, PPARγ

Référence

J. Physiol. Biochem.. 2020 Jun 26;: