AB1395 UROLITHIN A AND B ACCELERATE MYOCYTE FUSION INTO MYOTUBES

Background Urolithins are intestinal bacterial metabolites of ellagic acid, from pomegranate and nuts. They modulate oxidative-regulated pathways display anti-inflammatory, antioxidative properties. Several studies indicate that they could be inducers muscle strengthening. Objectives The aim this in vitro study was to investigate their mechanisms action at plasma concentrations on primary human myotubes. Methods Urolithin A B (UA UB) were evaluated separately CD56+ cells, isolated the vastus lateralis 6 men 3 women (aged range 55 96-y) differentiated 24h-treatment mRNA-sequencing these 9 patients studied by DESeq2 analysis (R software). Modulation several target genes then validated (1-5 or 10 µM) RT-qPCR ELISA 4 different patients. Organelles cell morphology changes observed NanoLive CX-A live imaging during 72h. Results After 24h treatment 5 µM, UA UB significantly modified expression 1779 319 genes, respectively (adjusted p-value 0.01 Log2FoldChange |>0.32|). Among most regulated we found involved myoblasts myotubes differentiation. increased MYMX (+70%), PANX1 (+50%), MSTN (+64%), MYH2 (+28%) conversely decreased FGF9 (-75%), MRLN (-33%), ICAM5 (-52%) TGFBI (-55%). Regarding UB, it IGFN1 (-60%) (+34%) TGM2 (+59%). However, UA, but not DMD gene (-86%), a key factor strength, MEF2C (-45%), regulator skeletal myogenesis. We also have modulation inflammatory process. both induced important decrease CYP1B1 (-95%). Further, LIF 80% PTGS1 41% 43% UB. had opposite effect IL17B, cytokine tissue repair its role is still defined. IL17B 49% upregulated 45% In second step, confirmed MYMX, PANX1, FGF9, ICAM5, PTGS1-PGE2, following and/or 1, µM ELISA. Finally, with myocyte fusion myotubes, already after 6h treatment. Conclusion promote differentiation process parallel, urolithins present anti-inflammatory properties, mainly reducing PGE2 synthesis via PTGS1, for increasing LIF. Our data provide better understanding urolithin activities highlight potential disorders such as sarcopenia. References NA. Acknowledgement would like thank staff GIGA ULiège Genomic Next Generation Sequencing platform performing RNA sequencing CIRM IN VITRO-SANTE imaging. Disclosure Interests Yves Henrotin Consultant of: Artialis SA Nestlé Expanscience Tilman Allegro Immubio, Cécile Lambert: None declared, Antoine Florin: Jérémie Zappia: Prescilia Centonze: christelle sanchez: declared.