NC1184: Molecular Mechanisms Regulating Skeletal Muscle Growth and Differentiation

One of the longest standing regional projects, the NC1184 group consists of 26 member agriculture experiment stations with a rich history of benchtop discovery in muscle biology with translation to the meat and livestock production sectors. The multidisciplinary efforts are focused on 1) The molecular mechanisms controlling skeletal muscle tissue growth, development and composition. Muscle stem cells, commonly referred to as satellite cells, are intimate to both pre- and post-natal muscle formation and hypertrophy. Normally found in a quiescent state, SCs become mitotically active, proliferate and fuse with the adjacent muscle fiber. Manipulation of SC bioactivity through environmental and dietary cues can impact lean tissue accretion in livestock and poultry. The Ohio State station provide evidence that heat stress causes lipid accumulation in turkey SC in an mTOR-dependent manner (Xu et al., 2022). Controlling the early post-hatch temperature may offer a unique means of altering muscle composition later in life. In a similar manner, supplementation of hen diets with micronutrients or injection of vitamin precursors into the fertilized egg are promising growth modifiers. The Alabama station demonstrate that supplementation of hen diets with calcidiol, a vitamin D metabolite, increased SC proliferation in the chick leading to a larger breast muscle (Avila et al., 2022). Providing nicotinamide riboside, a form of vitamin B3 and NAD precursor, to broiler embryos via in ovo yolk injection results in a greater number of fibers per unit area in the pectoralis muscle at hatch (Xu et al., 2022). These 2 papers demonstrate the importance of micronutrients to SC activity and muscle growth. The mechanism(s) mediating SC proliferation and differentiation are complex and involve both intracellular signaling systems and transcriptional responses (Engquist and Zammit, 2021). In a cross-species survey of mitochondria activity, the Nebraska group demonstrates that signals that modify metabolism may also lead to altered SC myogenesis (Sieck et al., 2022). Fresh isolates of bovine, ovine and porcine SC were treated with beta-adrenergic agonists (BAA) and oxidative phosphorylation parameters were measured. The results demonstrate that the commercial BAAs increase maximal respiration in bovine SC but not in their ovine or porcine counterparts. These efforts may partially explain differences in live animal and carcass responses exhibited by the cattle and pigs fed BAA. 2) Signal transduction pathways that regulate skeletal muscle metabolism. Muscle is the largest tissue in the body with large metabolic demands during growth and hypertrophy. The heterogeneous tissue is classified by the individual cells propensity to use either glycolytic or oxidative pathways for ATP generation. The substrates, metabolites and interplay between these energy systems determines not only the extent of muscle growth but also plays an important role in homeostasis (Zumbaugh et al., 2022). Metabolic flexibility, the ability to adapt and use the available fuel supply, is disrupted in the muscle of pigs experiencing heat stress (Zhao et al., 2018; Fausnacht et al., 2021). Unable to efficiently use fatty acids for energy production, heat stressed pigs rely on carbohydrates to meet the ATP demands during muscle growth. The Virginia station reports that feeding an artificial sweetener and capsaicin to heat-stressed pigs prevented the loss of metabolic flexibility but was insufficient to restore growth rates to levels comparable to thermoneutral controls (Kroscher et al., 2022). The ability of the countermeasure to affect muscle metabolism may have beneficial effects in other production settings experiencing stressors that restrict growth. Perturbations in maternal or fetal nutrient abundance can lead to reduced energy substrates available to support in utero fetal muscle growth and function. Over and under feeding pregnant ewes causes a reduction in the abundance of multiple proteins involved in mRNA translation and protein turnover in the fetus after 60-days of the dietary insult with continued altered expression patterns throughout gestation (Reed et al., 2022). The negative consequences of reduced nutrients to the fetus have lifelong effects that include predisposition to poor health and disease. The Nebraska station reports that myoblasts isolated from intrauterine growth restricted fetuses form myotubes in vitro that express greater amounts of TNFα receptor mRNA leading to greater amounts of phosphoNFκB following stimulation with TNFα (Posont et al, 2022). Thus, cytokine signaling contributes to the altered muscle size and metabolism found in growth-restricted individuals. 3) Mechanisms of protein synthesis and degradation in skeletal muscle. With the rising global population, a greater emphasis on meat production is required to satisfy rising nutritional demands (Leroy et al., 2022). Muscle is an excellent source of high-quality protein, vitamins and minerals supplying required nutrients above those found in plant-based diets (van Vliet et al., 2015). Efficient accretion of muscle protein can be promoted by feeding BAA or by administration of hormone-secreting implants, such as trenbolone acetate (TBA) (Dilger et al., 2021; Messersmith et al., 2021). The means by which TBA accomplishes this attributed to altered SC activity and protein turnover (Dayton and White, 2014). The Utah station provides a manuscript indicating that 10-day of TBA release is insufficient to alter SC marker gene expression (Reichardt et al., 2022). However, the breed of cattle receiving the growth promotant affects muscle responses with calpastatin expression greater in Bos indicus influenced cattle by comparison to Bos taurus. Calpastatin, an inhibitor of calpain enzymes, slow myofibrillar protein degradation leading to reduced meat tenderness (Warner et al., 2021). The Utah station builds upon this concept by finding that very tender beef steaks contain fewer intact contractile proteins by comparison to those of intermediate tenderness (Dang et al., 2022). Intermediate tenderness steaks contained greater amounts of calcium-binding proteins that may have limited calpain activities and greater amounts of connective tissue. These select papers and others from the NC1184 group can be found in this issue of the Journal of Animal Science.