Macaluso F

Satellite cell count, VO2max, and p38 MAPK in inactive to moderately active young men

Satellite cells (SCs) are responsible for muscle repair following strenuous exercise or injury. SC responses to intervention have been studied, but most studies do not discuss or take into account the substantial variability in SC number among young individuals. We hypothesized that an active lifestyle reflected in higher VO2max may be associated with greater SC number. As training alters basal p38‐mitogen‐activated protein kinase (MAPK) activity, which is associated with SC proliferation, SC count may also correlate with this stress signaling kinase. Muscle biopsies from vastus lateralis of eight male participants were analyzed for fiber type, myogenin, and p38/phospho‐p38 MAPK using SDS‐PAGE and Western blotting. Immunofluorescence was used to detect Pax7+ SCs. Two weeks following the biopsy, subjects underwent an incremental treadmill test to determine VO2max. A strong positive correlation (Pu2009=u20090.0087) was found between the number of Pax7+ nuclei and VO2max. Pax7+ cell number correlated negatively with phospho‐p38/p38 MAPK (Pu2009=u20090.0006), but had no correlation with fiber type or myogenin. SC number is proportional to VO2max, and hence it can be postulated that higher levels of physical activity activate SC proliferation but not fusion, underlining the relevance of exercise in stimulating SC pool size even without injury.

Acute change of titin at mid-sarcomere remains despite 8 wk of plyometric training

The purpose of this study was to investigate skeletal muscle changes induced by an acute bout of plyometric exercise (PlyEx) both before and after PlyEx training, to understand if titin is affected differently after PlyEx training. Healthy untrained individuals (N = 11) completed the 1stPlyEx (10 × 10 squat-jumps, 1-min rest). Thereafter, six subjects completed 8 wk of PlyEx, while five controls abstained from any jumping activity. Seven days after the last training session, all subjects completed the 2ndPlyEx. Blood samples were collected before and 6 h and 1, 2, 3, and 4 days after each acute bout of PlyEx, and muscle biopsies 4 days before and 3 days after each acute bout of PlyEx. The 1stPlyEx induced an increase in circulating myoglobin concentration. Muscle sample analysis revealed Z-disk streaming, a stretch or a fragmentation of titin (immunogold), and increased calpain-3 autolysis. After training, 2ndPlyEx did not induce Z-disk streaming or calpain-3 activation. The previously observed post-1stPlyEx positional change of the titin COOH terminus was still present pre-2ndPlyEx, in all trained and all control subjects. Only two controls presented with Z-disk streaming after 2ndPlyEx, while calpain-3 activation was absent in all controls. Eccentric explosive exercise induced a stretch or fragmentation of titin, which presented as a positional change of the COOH terminus. Calpain-3 activation does not occur when titin is already stretched before explosive jumping. Enzymatic digestion results in titin fragmentation, but since an increase in calpain-3 autolysis was visible only after the 1stPlyEx acute bout, fragmentation cannot explain the prolonged positional change.

Satellite cell pool expansion is affected by skeletal muscle characteristics

Introduction: We investigated changes in satellite cell (SC) pool size after an acute bout of strenuous exercise and evaluated the influence of baseline SC count and fiber type. Methods: Participants completed a downhill running (DHR) intervention (5 × 8 min, 2‐min rest; 80% VO2max; −10% gradient). Muscle biopsies were taken 7 days before VO2max and 7–9 days after the DHR intervention. Delayed‐onset muscle soreness (DOMS) and creatine kinase activity (CK) were measured on days 1, 2, 7, and 9 post‐DHR. SCs were identified by Pax7 and laminin staining. Relative distribution of MHC isoforms was determined by electrophoresis. Results: DOMS and CK peaked on day 1 post‐DHR (P < 0.01). The SC pool increased (26%) after DHR (P = 0.005). SCs/total myonuclei after recovery correlated with baseline SCs (r = 0.979, P = 0.003) and VO2max (r = 0.956, P = 0.011), whereas change in SC pool (Pax7+ cells/total myonuclei: recovery minus baseline) tended to correlate with percent MHC II (r = 0.848; P = 0.06). Conclusion: Interindividual physiological characteristics affect SC pool expansion after a single bout of DHR and are influenced by VO2max. Muscle Nerve, 2013

Silybin enhances mitochondrial function and inhibits NFkB activation in murine nonalcoholic fatty liver disease

background & Aims Non Alcoholic Fatty Liver Disease (NAFLD) is a chronic liver disease with possible cirrhotic and tumorigenic evolution. Despite a number of treatment has been proposed for NAFLD, none of these is really satisfying. Silybin, a flavonolignan extracted from milk thistle, showed marked liver protecting action in a variety of liver injury and is used as hepatoprotectant. We aimed to clarify the putative therapeutic significance of silybin and to identify the molecular pathways of silybinmediated hepatoprotection in a murine model of NAFLD. Methods We explored the effect of a 4-week daily (20mg/kg i.p.) administration of silybin in 6-week-old db/db mice feeding a methionine-choline deficient (MCD) diet. We examined liver histology, hepatic lipid homeostasis, mitochondrial function, oxidative-nitrosative stress and NFkB activation in silybin-treated mice compared with untreated animals. Results Silybin markedly decreased serum ALT and liver triglycerides content. Steatosis was less severe in grade and distribution, and lobular inflammation was almost absent in silybin-treated mice. At the molecular level, silybin promoted the gene expression of key enzymes involved in free fatty acids elongation and β-oxidation and completely restores mitochondrial respiratory chain activity. Furthermore, silybin markedly decreased oxidative-nitrosative stress and inhibited NFkB p65 and p50 subunits binding activity. Conclusions In the current study we showed that silybin displayed a marked antisteatotic and anti-inflammatory effect in the db/db + MCD murine model of NAFLD. In our opinion, these findings provide the rationale for the use of silybin in the clinical management of patients with NAFLD, which will require well-designed clinical trials.