Regulation of Muscle Growth in Early Postnatal Life in a Swine Model

Skeletal muscle growth during the early postnatal period is rapid in the pig and dependent on the capacity of muscle to respond to anabolic and catabolic stimuli. Muscle mass is driven by the balance between protein synthesis and degradation. Among these processes, muscle protein synthesis in the piglet is exceptionally sensitive to the feeding-induced postprandial changes in insulin and amino acids, whereas muscle protein degradation is affected only during specific catabolic states. The developmental decline in the response of muscle to feeding is associated with changes in the signaling pathways located upstream and downstream of the mechanistic target of rapamycin protein complex. Additionally, muscle growth is supported by an accretion of nuclei derived from satellite cells. Activated satellite cells undergo proliferation, differentiation, and fusion with adjacent growing muscle fibers. Enhancing early muscle growth through modifying protein synthesis, degradation, and satellite cell activity is key to maximizing performance, productivity, and lifelong pig health.

Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice

Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a nondamaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low-impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice ( n = 6/group) were randomly placed into five groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: nonsuspended mouse cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation was evaluated by providing mice 5-bromo-2′-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force, decreased in vivo fatigability, and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type I and IIa MHC abundance, increased fiber cross-sectional area, and increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7-positive nuclei inside muscle fibers and a greater MyoD-to-Pax 7 protein ratio compared with HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR mice had lower levels of the inactive phosphorylated YAPserine127, which may have contributed to increased satellite cell activation with reloading after HSU. These results indicate that voluntary wheel running increased YAP signaling and satellite cell activity after HSU and this was associated with improved recovery. NEW & NOTEWORTHY Although satellite cell involvement in muscle remodeling has been challenged, the data in this study suggest that voluntary wheel running increased satellite cell activity and suppressed Yes-associated protein (YAP) protein relative to no wheel running and this was associated with improved muscle recovery of force, fatigue resistance, expression of type I myosin heavy chain, and greater fiber cross-sectional area after disuse.

Loss of Ptpn11 (Shp2) drives satellite cells into quiescence

The equilibrium between proliferation and quiescence of myogenic progenitor and stem cells is tightly regulated to ensure appropriate skeletal muscle growth and repair. The non-receptor tyrosine phosphatase Ptpn11 (Shp2) is an important transducer of growth factor and cytokine signals. Here we combined complex genetic analyses, biochemical studies and pharmacological interference to demonstrate a central role of Ptpn11 in postnatal myogenesis of mice. Loss of Ptpn11 drove muscle stem cells out of the proliferative and into a resting state during muscle growth. This Ptpn11 function was observed in postnatal but not fetal myogenic stem cells. Furthermore, muscle repair was severely perturbed when Ptpn11 was ablated in stem cells due to a deficit in stem cell proliferation and survival. Our data demonstrate a molecular difference in the control of cell cycle withdrawal in fetal and postnatal myogenic stem cells, and assign to Ptpn11 signaling a key function in satellite cell activity.

Methionine concentration in the pre-starter diet: its effect on broiler breast muscle development

The effect of feeding diets of variable methionine concentration on breast muscle development was assessed in Ross 308 broiler chicks. Four isonitrogenous and isoenergetic starter diets were formulated to contain 7.8, 5.9, 4.6, and 3.4 g methionine/kg diet, and were provided for the first 7 days post-hatch. At 7 days of age all birds were placed on an industry standard starter diet with 5.9 g methionine/kg diet until 14 days, and then provided standard broiler grower (until 28 days) and finisher (until 42 days) diets. Birds were weighed periodically throughout the study and feed intake and feed conversion ratio were determined. Ten birds per treatment were sacrificed and weighed on 0, 1, 4, 7, 14, 21, 28, 35, and 42 days. The pectoralis major (breast muscle) was then removed from the carcass and weighed. Samples of breast muscle were collected for genetic and histological analysis. Expression of the myogenic marker genes, myogenic differentiation factor 1 and myogenin, which regulate satellite cell activity, and the adipogenic marker gene, peroxisome proliferator-activated receptor gamma (PPARγ), was measured. Histological assessment of breast muscle morphology and fat deposition morphology was also performed. No effect of dietary treatment was observed on body or breast muscle weight, feed intake or feed conversion ratio. Marker gene expression was also similar in all treatment groups, except for PPARγ. Significantly higher expression of PPARγ was observed at 0 days in the 5.9 g methionine/kg diet treatment, before dietary treatments were provided. Expression of PPARγ did not differ among treatment groups on any subsequent day. Methionine dietary treatment had no effect on the morphological structure of the breast muscle, or intramuscular fat deposition. These results suggest that under the conditions of this study, satellite cell activity in the early post-hatch chick, and subsequent muscle development, were not responsive to the variable methionine manipulations tested in the pre-starter period.