Musclin gene expression is strongly related to fast-glycolytic phenotype

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Abstract

Musclin has been described as a muscle-derived secretory peptide, responsive to insulin in vivo, and inducing insulin resistance in vitro. Because muscle fibers display very different metabolic properties and insulin sensitivity, we tested the hypothesis that musclin expression could depend on myofiber type. Musclin mRNA was detected at high level in fast gastrocnemius and plantaris muscles, but only as traces in soleus, a slow-twitch muscle. A single fiber analysis showed that musclin was produced by muscle fibers themselves, almost exclusively type IIb fibers. Slow to fast transition of soleus phenotype after hindlimb suspension increased musclin mRNA levels, whereas fast to slow transition of plantaris phenotype after functional overload decreased musclin mRNA levels. This clearly suggests that musclin transcription is strongly related to fast-glycolytic phenotype. We conclude that musclin is produced by myocytes in a highly fiber-type specific manner and that physiological changes in type IIb MHC lead to coordinated musclin expression.

Section snippets

Methods

Animals. Experiments were carried out in accordance with the Helsinki Accords for Human Treatment of Animals during Experimentation. Wistar rats were housed with free access to food and water. Animals were studied at rest (control experiment) or after either mechanical unloading or overload. For the unloading protocol, we used the tail-suspension model, a valid model of removal of weight-bearing activity of soleus muscle [13]. Rats were hindlimb suspended for 3 weeks and then sacrificed. The

Whole muscle musclin mRNA in control animals

In soleus muscles, musclin mRNA levels were only detectable as traces. In contrast, musclin mRNA levels were markedly higher in plantaris and at a 2.2-fold higher level in gastrocnemius muscles than in plantaris (P < 0.01) (Fig. 1).

Musclin mRNA levels within single pure fibers

Musclin mRNA levels were only examined in pure fiber types, those expressing only one MHC isoform at the protein level (about 40% of all isolated single fibers). As shown in Fig. 2, musclin mRNA expression was highly fiber-type specific (main effect P < 0.001). Musclin

Discussion

The control of musclin expression as well as the exact function of this new muscle-derived factor remain largely unknown. The present study has investigated the fiber-type specificity of musclin expression and whether its transcription is coordinated with phenotypic changes. Results show that (1) musclin mRNA is almost undetectable in the slow-twitch soleus muscle whereas high levels are found in the fast-twitch plantaris and white gastrocnemius muscles, (2) musclin is produced by muscle cells

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