Inefficient ATP synthesis by inhibiting mitochondrial respiration causes lipids to decrease in MSTN-lacking muscles of loach Misgurnus anguillicaudatus.

Abstract

Myostatin (MSTN) lacking could lead to enhanced muscle growth and lipid metabolism disorder in animals. Plenty of researches have been performed to warrant a better understanding of the mechanisms underlying the enhanced muscle growth; however, mechanisms for lipid metabolic changes are poorly understood. In this study, MSTN-depletion loaches Misgurnus anguillicaudatus (MU for short) were firstly generated by CRISPR/Cas9 technique. Based on histological observation, we found that skeletal muscle fat accumulation in MU sharply reduced compared with wild-type loaches (WT for short). To further investigate the fat change, muscle lipidomic analysis was performed. There were no significant differences in three membrane phospholipid contents between WT and MU. The contents of six other major lipid species in MU muscles were all significantly lower than those in WT muscles, indicating that MSTN deficiency could obviously decrease muscle lipid production in the loach. Meanwhile, it was also supported by results of three lipogenesis-related genes' expressions. And then combined with muscle ATP determination and gene expression profiles of the five mitochondrial respiration chain complexes, we speculated that MSTN lacking may cause the weak of mitochondrial respiration functions in the loach muscles, leading to ATP synthesis decreasing and finally reducing the production of lipids.