Transitions towards either slow-oxidative or fast-glycolytic phenotype can be induced in the murine WTt myogenic cell line

Contraction and energy metabolism are functions of skeletal muscles co‐regulated by still largely unknown signals. To help elucidating these interconnecting pathways, we are developing new cellular models that will allow to control the switch from a neonatal to an adult slow‐oxidative or fast‐glycolytic phenotype of myofibers, during in vitro differentiation. Thus, our purpose was to direct the differentiation of the newly characterized WTt clone, from a mixed towards either fast or slow phenotype, by modifying amounts of two transcription factors respectively involved in control of glycolytic and oxidative energy metabolism, namely HIF‐1α and PPARδ. Our data support the idea that HIF‐1α protein stabilization would favor expression of fast phenotypic markers, accompanied or not by a decreased expression of slow markers, depending on treatment conditions. Conversely, PPARδ over‐expression appears to enhance the slow‐oxidative phenotype of WTt myotubes. Furthermore, we have observed that expression of PGC‐1α, a coregulator of PPAR, is also modified in this cell line upon conditions that stabilize HIF‐1α protein. This observation points to the existence of a regulatory link between pathways controlled by the two transcription factors HIF‐1α and PPARδ. Therefore, these cells should be useful to analyze the balance between oxidative and glycolytic energy production as a function of phenotypic transitions occurring during myogenic maturation. The newly characterized murine WTt clone will be a good tool to investigate molecular mechanisms implicating HIF‐1α and PPARδ in the coordinated metabolic and contractile regulations involved in myogenesis. J. Cell. Biochem. 111: 82–93, 2010. © 2010 Wiley‐Liss, Inc.