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

Abstract

SUMMARYSkeletal 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. KEYWORDSSingle myofiber, skeletal muscle metabolism, mitochondria, miRNAs, lipids. 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 peer-reviewed)

The epigenetic landscape in purified myonuclei from fast and slow muscles

“…The transcription factors PPARA and Estrogen Related Receptor Beta (ESRRB) are mediating fatty acid degradation and oxidative metabolism (73,103,104). Similar roles are known for additional members of their respective families (105,106).…”

“…The sorting is important since only less than 60% of the cell nuclei in muscle tissue are myonuclei (22,24), and the sorting excluded When we compared myonuclei from the two extreme muscles soleus and EDL we found that they had a large part of the epigenome in common. Important differences were found in connection to genes coding for proteins involved in contraction, calcium handling and metabolic pathways; reflecting differences at the transcriptional and protein level between different fiber types (41,64,(73)(74)(75).…”