miR-130a-3p promotes fiber type transition and improves exercise tolerance in mice

TL;DR

miR-130a-3p improves muscle endurance and metabolism in mice by changing muscle fiber types and targeting the TGFβR2 pathway.

Contribution

miR-130a-3p is shown to regulate muscle fiber type transition and energy metabolism via TGFβR2 signaling.

Findings

miR-130a-3p overexpression increases type I fibers and decreases type IIB fibers in mouse gastrocnemius.

miR-130a-3p inhibits myoblast differentiation and promotes proliferation by targeting TGFβR2.

miR-130a-3p improves exercise tolerance and reduces fat content in mice.

Abstract

Skeletal muscle plays various roles in physiological stress, such as movement, hormone secretion and oxidative metabolism. MicroRNA (miRNA) is involved in skeletal muscle development and fiber type transformation. Our previous studies have shown that miR-130a-3p is an important regulator of glycolipid metabolism and participates in the aerobic oxidation process. However, its potential impact on skeletal muscle development and muscle fiber type transformation by enhancement of aerobic metabolism of nutrients remains unexplored.

Mice with knockout and overexpression of miR-130a-3p were utilized to investigate its impact on mouse muscle development via assessments of body composition, metabolic activity in cages, and running performance. The influence of miR-130a-3p on muscle cell proliferation, differentiation, and fiber type was assessed following transfection of C2C12 cells.

In this study, we found that miR-130a-3p overexpression significantly inhibited weight gain and fat content in mice, while promoting oxidative metabolism and improving exercise tolerance. Upregulation of miR-130a-3p in gastrocnemius (GAS) increased the expression of genes controlling cell proliferation, such as proliferating cell nuclear antigen (PCNA), cyclin D, and cyclin E, and decreased the protein expression of myosin heavy chain (MyHC), myogenic differentiation 1 (MyoD) and myopoietin (MyoG). In addition, miR-130a-3p overexpression significantly increased the proportion of type I fibers and decreased the proportion of type IIB fibers in GAS. These phenotype were also observed when miR-130a-3p was overexpressed in differentiated C2C12 myoblasts. Mechanistically, miR-130a-3p can promote the proliferation of myoblasts and inhibit the differentiation of myoblasts. Importantly, miR-130a-3p was proved to target the transforming growth factor beta receptor 2 (TGFβR2). Taken together, miR-130a-3p could be a potential therapeutic target that regulates fiber type conversion during skeletal muscle development and improves skeletal muscle energy metabolism during exercise through regulating TGFβR2 signalling pathway.

Figures