A Specific microRNA Targets an Elongase of Very Long Chain Fatty Acids to Regulate Fatty Acid Composition and Mitochondrial Morphology of Skeletal Muscle Cells

SIMPLE SUMMARY: Recently, it was found that miR-22 might be involved in the regulation of muscle tenderness and was an important miRNA that affects meat quality. In the present study, we demonstrated that miR-22 regulates the fatty acid composition and mitochondrial morphology of skeletal muscle cells by inhibiting ELOVL6 expression. This study presented the first systematical investigation on the miR-22 correlation with fatty acid composition and mitochondrial function in muscle cells. Our finding is important to help us to understand the function of miR-22 in skeletal muscle cells and the complicacy of muscle metabolism regulation. ABSTRACT: Recently, miR-22 has been suggested to be an important microRNA (miRNA) affecting meat quality. Studies have shown that muscle fatty acid composition and mitochondrial function are closely related to meat quality. The regulatory mechanism of miR-22 on skeletal muscle fatty acid composition and mitochondrial function is not well characterized. Therefore, we aimed to explore the effects of miR-22 on fatty acid composition and mitochondrial function in C2C12 cells. Here, it demonstrate that elevated expression of miR-22 significantly repressed fatty acid elongation and mitochondrial morphology in C2C12 myoblasts, while the knockdown of miR-22 showed opposite results. Furthermore, miR-22 targets the elongase of very long chain fatty acids 6 (ELOVL6) and represses its expression in muscle cells. Knockdown of ELOVL6 mimicked the effect of miR-22 on fatty acid composition and mitochondrial function, while overexpression of ELOVL6 restored the effects of miR-22. These findings indicate that miR-22 downregulates the elongation of fatty acids and mitochondrial morphology by inhibiting ELOVL6 expression in muscle cells, which may provide some useful information for controlling muscle lipid accumulation and mitochondrial function in livestock in the future.