Lipid utilization in skeletal muscle cells is modulated in vitro and in vivo by specific miRNAs

SUMMARY Skeletal muscle is composed by different myofiber types that can preferentially use glycolysis or lipids for ATP production. How fuel preference is specified in these post-mitotic cells is unknown. Here we show that miRNAs are important players in defining the myofiber metabolic profile. mRNA and miRNA signatures of all myofiber types obtained at single cell level unveiled fiber-specific regulatory networks and identified two master miRNAs that coordinately control myofiber fuel preference and mitochondrial morphology. Our work provides a complete and integrated myofiber type-specific catalogue of genes and miRNAs expressed and establishes miR-27a-3p and miR-142-3p as key regulators of lipid utilization in skeletal muscle. HIGHLIGHTS Transcriptional networking in single cells distinguished myofibers based on glycolytic or oxidative metabolism, regulated by specific miRNAs miR-27a-3p and −142-3p influence mitochondrial morphology miR-27a-3p improves lipid utilization and increases glycogen storage both in vitro and in vivo miR-142-3p reduces lipid utilization both in vitro and in vivo