Résumé :
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Communication n° 77. Wnt factors are secreted proteins that activate myogenesis, but repress adipogenesis, as disruption of Wnt signaling induced transdifferentiation of myoblasts into adipocytes. We reported de novo lipogenesis in contracting myotubes deriving from rat muscle satellite cells, leading to intramyocellular lipid synthesis. We showed that lipogenesis was dependent upon the expression of a lipogenic transcription factor, Sterol Regulatory Element Binding Protein-1c (SREBP-1c). To study the correlation between Wnt-signaling and SREBP-1c expression, we measured Wnt-10b and SREBP-1c protein levels in vivo during skeletal muscle ontogenesis or regeneration, as well as in vitro during satellite cell differentiation. In each condition, we showed an opposite expression profile for the two proteins. Wnt-10b increased by 10-fold from birth up to weaning, then became undetectable at the adult stage. In contrast, SREBP-1c was expressed only after weaning and increased in adult muscle. Similarly, Wnt-10b protein was drastically up-regulated two days after mechanical injury in EDL, whereas SREBP-1c protein expression was suppressed and remained undetectable throughout regeneration. In cultured satellite cells, Wnt-10b was strongly expressed in myoblasts, but no longer detectable in contracting myotubes, whereas SREBP-1c was dramatically expressed in these cells. Using specific siRNAs, we knocked-down SREBP-1c and observed 48 hours later the re-expression of Wnt-10b protein, that was concomitant with cytosolic beta-catenin activation and nuclear accumulation. Under these conditions, no intramyocellular lipid synthesis or accumulation occured. This shows that SREBP-1c knock-down was sufficient to re-activate Wnt-signaling in contracting myotubes, preventing them from deriving to an adipogenic-like phenotype. Whether increased lipogenesis observed in skeletal muscle with aging, obesity or type 2 diabetes could be due to alteration of the myogenic program remains to be determined.
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