Myosin relaxation states in skeletal muscle fibers of rats and mice: Effects of sex and adiposity

Myosin disordered- and super-relaxed states (DRX and SRX, respectively) in skeletal muscle fibers are hypothesized to play key roles in thermogenesis and basal metabolic energy expenditure, raising potential for novel therapeutic targets for obesity and other metabolic diseases. Limited studies have investigated relationships between body composition or biological sex and myosin relaxed states. Using fluorescence-based single-nucleotide turnover, we report quantitative relationships of diet-induced adiposity and sex with biochemical parameters of myosin relaxed states of rodent muscle fibers. Our main findings were: (1) adiposity had minimal to no effect on parameters of relaxed myosin states measured in fibers from rats and mice, (2) fibers from female rats and mice had 10%-20% shorter SRX lifetimes than those from males (p ≤ 0.035), (3) in rats, females had shorter DRX lifetimes than males, and (4) myosin heavy chain isoform had negligible impact on parameters of relaxed myosin states. We conclude that skeletal muscle energy utilization during rest, as measured by myosin ATPase, is affected minimally by adiposity, but differs by sex. Continued exploration of the metabolic implications of myosin transitioning between SRX and DRX will provide further understanding of muscle thermogenesis and whole-body metabolism; in so doing, sex as a biological factor should be considered.