Normal muscle fiber type distribution is recapitulated in aged ephrin-A3-/- mice that previously lacked most slow myofibers.

Individual limb muscles have characteristic representation and spatial distribution of muscle fiber types (one slow and up to three fast isoforms) appropriate to their unique anatomical location and function. This distribution can be altered by physiological stimuli such as training (i.e., for increased endurance or force) or pathological conditions such as aging. Our group previously showed that ephrin-A3 is expressed only on slow myofibers, and that adult mice lacking ephrin-A3 have dramatically reduced numbers of slow myofibers due to postnatal innervation of previously slow myofibers by fast motor neurons. In this study, fiber type composition of hindlimb muscles of aged and denervated/reinnervated C57BL/6 and ephrin-A3-/- mice was analyzed to determine whether the loss of slow myofibers persists across the lifespan. Surprisingly, fiber-type composition of ephrin-A3-/- mouse muscles at two years of age was nearly indistinguishable from age-matched C57BL/6 mice. After challenge with nerve crush, the percentage of IIa and I/IIa hybrid myofibers increased significantly in aged ephrin-A3-/- mice. While EphA8, the receptor for ephrin-A3, is present at all neuromuscular junctions (NMJs) on fast fibers in 3-6 mo old C57BL/6 and ephrin-A3-/- mice, this exclusive localization is lost with aging, with EphA8 expression now found on a subset of NMJs on some slow muscle fibers. This return to appropriate fiber-type distribution given time and under use reinforces the role of activity in determining fiber-type representation and suggests that, rather than being a passive baseline, the developmentally and evolutionarily selected fiber type pattern may instead be actively reinforced by daily living.

Role of PGC-1α in fiber type conversion in the palatopharyngeus muscle of OSA patients.

BACKGROUND: Obstructive sleep apnea (OSA) has a high incidence and is harmful to health. It is characterized by repeated collapse of the upper airway. However, the mechanism underlying upper airway collapse is unclear. METHODS: Patients with OSA and chronic tonsillitis were studied. Pathological changes in palatopharyngeus muscle were detected. The expression of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) and nuclear respiratory factor-1 (NRF-1) in muscles was detected by PCR and Western blotting. Immunofluorescence staining was used to detect the expression of type I and type II myofibril. RESULTS: The structure of the palatopharyngeus muscle was changed, and the expression of PGC-1α and NRF-1 was decreased in the OSA group compared with that in the control group. The expression of PGC-1α, NRF-1, and type I myofibril in C2C12 myoblasts was decreased by intermittent hypoxia exposure. The expression of type I myofibril was decreased when knocking down PGC-1α. CONCLUSION: OSA patients exhibited pathological damage in palatopharyngeus muscle. PGC-1α was involved in the fiber type conversion in palatopharyngeus muscle caused by intermittent hypoxia.

miR-22-3p regulates muscle fiber-type conversion through inhibiting AMPK/SIRT1/PGC-1α pathway.

MicroRNAs (miRNAs) are a class of conserved non-coding RNAs that are widely regarded as important regulators in a variety of biological processes. Increasing evidence has revealed that skeletal muscle fiber-type conversion is regulated by miRNAs, but the molecular mechanism is still not fully understood. In this study, we confirmed the role of miR-22-3p on skeletal muscle fiber-type conversion and investigated its potential mechanism in C2C12 myotubes. Here, we found that the miR-22-3p mimics inhibited the expressions of myosin heavy chain I (MyHC I), MyHC IIa and promoted the expression of MyHC IIb, while miR-22-3p inhibitor got inverse results. miR-22-3p mimics also downregulated phosphorylated AMPK, SIRT1 and PGC-1ɑ protein levels, which control the expression of oxidative fiber-related genes. Furthermore, Compound C (AMPK inhibitor) eliminated the effect of miR-22-3p inhibitor on MyHC I, MyHC IIa and MyHC IIb expressions. However, AICAR (AMPK activator) also abolished the effect of miR-22-3p mimics on MyHC I, MyHC IIa and MyHC IIb expressions. Collectively, our results suggest that miR-22-3p regulates skeletal muscle fiber-type conversion through inhibiting AMPK/SIRT1/PGC-1ɑ signaling pathway.

Skeletal muscle fiber analysis by atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometric imaging at high mass and high spatial resolution.

Skeletal muscles are composed of heterogeneous muscle fibers with various fiber types. These fibers can be classified into different classes based on their different characteristics. MALDI mass spectrometric imaging (MSI) has been applied to study and visualize different metabolomics profiles of different fiber types. Here, skeletal muscles were analyzed by atmospheric pressure scanning microprobe MALDI-MSI at high spatial and high mass resolution.

Action potential amplitude as a noninvasive indicator of motor unit-specific hypertrophy.

Skeletal muscle fibers hypertrophy in response to strength training, with type II fibers generally demonstrating the greatest plasticity in regards to cross-sectional area (CSA). However, assessing fiber type-specific CSA in humans requires invasive muscle biopsies. With advancements in the decomposition of surface electromyographic (sEMG) signals recorded using multichannel electrode arrays, the firing properties of individual motor units (MUs) can now be detected noninvasively. Since action potential amplitude (APSIZE) has a documented relationship with muscle fiber size, as well as with its parent MU's recruitment threshold (RT) force, our purpose was to examine if MU APSIZE, as a function of its RT (i.e., the size principle), could potentially be used as a longitudinal indicator of MU-specific hypertrophy. By decomposing the sEMG signals from the vastus lateralis muscle of 10 subjects during maximal voluntary knee extensions, we noninvasively assessed the relationship between MU APSIZE and RT before and immediately after an 8-wk strength training intervention. In addition to significant increases in muscle size and strength (P < 0.02), our data show that training elicited an increase in MU APSIZE of high-threshold MUs. Additionally, a large portion of the variance (83.6%) in the change in each individual's relationship between MU APSIZE and RT was explained by training-induced changes in whole muscle CSA (obtained via ultrasonography). Our findings suggest that the noninvasive, electrophysiological assessment of longitudinal changes to MU APSIZE appears to reflect hypertrophy specific to MUs across the RT continuum.

Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds.

PURPOSE OF REVIEW: The global obesity epidemic has become a major public health concern, necessitating comprehensive research into its adverse effects on various tissues within the human body. Among these tissues, skeletal muscle has gained attention due to its susceptibility to obesity-related alterations. Mitochondria are primary source of energy production in the skeletal muscle. Healthy skeletal muscle maintains constant mitochondrial content through continuous cycle of synthesis and degradation. However, obesity has been shown to disrupt this intricate balance. This review summarizes recent findings on the impact of obesity on skeletal muscle mitochondria structure and function. In addition, we summarize the molecular mechanism of mitochondrial quality control systems and how obesity impacts these systems. RECENT FINDINGS: Recent findings show various interventions aimed at mitigating mitochondrial dysfunction in obese model, encompassing strategies including caloric restriction and various dietary compounds. Obesity has deleterious effect on skeletal muscle mitochondria by disrupting mitochondrial biogenesis and dynamics. Caloric restriction, omega-3 fatty acids, resveratrol, and other dietary compounds enhance mitochondrial function and present promising therapeutic opportunities.

Dietary short-term supplementation of grape seed proanthocyanidin extract improves pork quality and promotes skeletal muscle fiber type conversion in finishing pigs.

Plant extracts are commonly used as feed additives to improve pork quality. However, due to their high cost, shortening the duration of supplement use can help reduce production costs. In this study, we aimed to investigate the effects of grape seed proanthocyanidin extract (GSPE) on meat quality and muscle fiber characteristics of finishing pigs during the late stage of fattening, which was 30 days in our experimental design. The results indicated that short-term dietary supplementation of GSPE significantly reduced backfat thickness, but increased loin eye area and improved meat color and tenderness. Moreover, GSPE increased slow myosin heavy chain (MyHC) expression and malate dehydrogenase (MDH) activity, while decreasing fast MyHC expression and lactate dehydrogenase (LDH) activity in the Longissimus thoracis (LT) muscle. Additionally, GSPE increased the expression of Sirt1 and PGC-1α proteins in the LT muscle of finishing pigs and upregulated AMP-activated protein kinase α 1 (AMPKα1), AMPKα2, nuclear respiratory factor 1 (NRF1), and calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß) mRNA expression levels. These findings suggest that even during the late stage of fattening, GSPE treatment can regulate skeletal muscle fiber type transformation through the AMPK signaling pathway, thereby affecting the muscle quality of finishing pigs. Therefore, by incorporating GSPE into the diet of pigs during the late stage of fattening, producers can enhance pork quality while reducing production costs.

The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats.

Introduction: Skeletal muscle insulin resistance (IR) plays an important role in the pathogenesis of type 2 diabetes mellitus. Skeletal muscle is a heterogeneous tissue composed of different muscle fiber types that contribute distinctly to IR development. Glucose transport shows more protection in slow-twitch muscles than in fast-twitch muscles during IR development, while the mechanisms involved remain unclear. Therefore, we investigated the role of the mitochondrial unfolded protein response (UPRmt) in the distinct resistance of two types of muscle in IR. Methods: Male Wistar rats were divided into high-fat diet (HFD) feeding and control groups. We measured glucose transport, mitochondrial respiration, UPRmt and histone methylation modification of UPRmt-related proteins to examine the UPRmt in the slow fiber-enriched soleus (Sol) and fast fiber-enriched tibialis anterior (TA) under HFD conditions. Results: Our results indicate that 18 weeks of HFD can cause systemic IR, while the disturbance of Glut4-dependent glucose transport only occurred in fast-twitch muscle. The expression levels of UPRmt markers, including ATF5, HSP60 and ClpP, and the UPRmt-related mitokine MOTS-c were significantly higher in slow-twitch muscle than in fast-twitch muscle under HFD conditions. Mitochondrial respiratory function is maintained only in slow-twitch muscle. Additionally, in the Sol, histone methylation at the ATF5 promoter region was significantly higher than that in the TA after HFD feeding. Conclusion: The expression of proteins involved in glucose transport in slow-twitch muscle remains almost unaltered after HFD intervention, whereas a significant decline of these proteins was observed in fast-twitch muscle. Specific activation of the UPRmt in slow-twitch muscle, accompanied by higher mitochondrial respiratory function and MOTS-c expression, may contribute to the higher resistance to HFD in slow-twitch muscle. Notably, the different histone modifications of UPRmt regulators may underlie the specific activation of the UPRmt in different muscle types. However, future work applying genetic or pharmacological approaches should further uncover the relationship between the UPRmt and insulin resistance.

Dietary lycopene supplementation improves meat quality, antioxidant capacity and skeletal muscle fiber type transformation in finishing pigs.

This study aimed to investigate effects of dietary lycopene supplementation on meat quality, antioxidant ability and muscle fiber type transformation in finishing pigs. In a 70-day experiment, 18 Duroc × Landrace × Yorkshire barrows were randomly allocated to 3 dietary treatments including a basal diet supplemented with 0, 100 and 200 mg/kg lycopene, respectively. Each dietary treatment had 6 replicates with one pig each. Results showed that dietary 200 mg/kg lycopene supplementation increased muscle redness a∗ value, intramuscular fat and crude protein contents, and decreased muscle lightness L∗ and yellowness b∗ values (P < 0.05), suggesting that addition of 200 mg/kg lycopene to the diet of finishing pigs improved color, nutritional value and juiciness of pork after slaughter. Results also showed that dietary lycopene supplementation enhanced antioxidant capacity of finishing pigs (P < 0.05). Moreover, dietary supplementation of 200 mg/kg lycopene significantly increased slow myosin heavy chain (MyHC) protein level and slow-twitch fiber percentage, and decreased fast MyHC protein level and fast-twitch fiber percentage (P < 0.05), suggesting that the addition of 200 mg/kg lycopene to the diet of finishing pigs promoted muscle fiber type conversion from fast-twitch to slow-twitch. Together, we provide the first evidence that dietary 200 mg/kg lycopene supplementation improves meat quality, enhances antioxidant capacity and promotes muscle fiber type transformation from fast-twitch to slow-twitch in finishing pigs.

Aerobic exercise training-induced follistatin-like 1 secretion in the skeletal muscle is related to arterial stiffness via arterial NO production in obese rats.

Follistatin-like 1 (FSTL1), which is mainly secreted from skeletal muscle and myocardium, upregulates protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) phosphorylation in vascular endothelial cells. It is unclear whether skeletal muscle- and myocardium-derived FSTL1 secretion induced by aerobic exercise training is involved in the reduction of arterial stiffness via arterial NO production in obese rats. This study aimed to clarify whether aerobic exercise training-induced FSTL1 secretion in myocardium and skeletal muscle is associated with a reduction in arterial stiffness via arterial Akt-eNOS signaling pathway in obese rats. Sixteen Otsuka Long-Evans Tokushima Fatty (OLETF) obese rats were randomly divided into two groups: sedentary control (OLETF-CON) and eight-week aerobic exercise training (treadmill for 60min at 25m/min, 5days/week, OLETF-AT). Eight Long-Evans Tokushima Otsuka (LETO) rats were used as a healthy sedentary control group. In OLETF-CON, serum FSTL1, arterial Akt and eNOS phosphorylation, and arterial nitrite/nitrate (NOx) levels were significantly lower, and carotid-femoral pulse wave velocity (cfPWV) was significantly greater than those in LETO. These parameters were improved in the OLETF-AT compared to the OLETF-CON. In the OLETF-AT, FSTL1 levels in slow-twitch fiber-rich soleus muscle were significantly greater than those in the OLETF-CON, but not in myocardium, fast-twitch fiber-rich tibialis anterior muscle, and adipose tissue. Serum FSTL1 levels were positively correlated with soleus FSTL1, arterial eNOS phosphorylation, and NOx levels and negatively correlated with cfPWV. Thus, aerobic exercise training-induced FSTL1 secretion in slow-twitch fiber-rich muscles may be associated with a reduction in arterial stiffness via arterial NO production in obese rats.

VEGF alleviates lower limb ischemia in diabetic mice by altering muscle fiber types.

Lower limb ischemia caused by diabetic foot (DF) is one of the most serious complications of diabetes. The therapeutic role of VEGF in DF is well documented. However, the mechanism for action of VEGF is still not clear. The present study aimed to explore the effects of VEGF-mediated skeletal muscle fiber type switch in angiogenesis and the treatment of DF. C57BL/6 mice housed in cages equipped with a voluntary running wheel were used to access VEGF protein level and citrate synthase activity (by ELISA) as well as muscle fiber type changes (by immunofluorescence) in the gastrocnemius muscle. C57BL/6 mice were fed on a high-fat diet for 6 weeks and then injected with streptozocin to induce diabetic lower limb ischemia model. Control adenovirus (Ad-GFP) or Ad-VEGF-GFP were then injected into the left gastrocnemius of the ischemic diabetic mice. Blood flow perfusion was examined by laser Doppler imaging at 1, 3, 7 and 14 days after adenovirus transduction. On day 14, all mice were anesthetized and sacrificed. VEGF expression levels, citrate synthase activity and muscle fiber type changes in the gastrocnemius muscle were assayed by ELISA and immunofluorescence analysis of myosin heavy chain IIa (MHCIIa) expression, respectively. Transwell assays were performed to determine whether VEGF-treated C2C12 myotubes played a role on tubule formation and migration of HUVECs. It was found that VEGF levels and citrate synthase activity were upregulated after voluntary exercise, along with the increased frequency of oxidized muscle fibers. Notably, adenovirus-mediated VEGF overexpression in the muscle also increased the frequency of oxidized (MHCIIa-positive) muscle fibers, enhanced citrate synthase activity and ameliorated lower limb ischemia in diabetic mice. VEGF treatment enhanced the phosphorylation of PI3K, Akt and AMPK (assayed by western blotting), as well as glucose consumption and metabolism (assayed by western blotting and glucose uptake assay), in the C2C12 myotubes. Interestingly, VEGF-treated C2C12 myotubes promoted the migration and tubule formation of HUVEC cells. The present findings suggest that skeletal muscle fiber conversion might be a potential approach for VEGF-mediated angiogenesis and disease treatment, which may provide new options for the prevention and treatment of DF.

Dietary Malic Acid Supplementation Induces Skeletal Muscle Fiber-Type Transition of Weaned Piglets and Further Improves Meat Quality of Finishing Pigs.

The aim of this study was to investigate effects of dietary malic acid supplementation on skeletal muscle fiber-type transition during nursery period and the subsequent meat quality of finishing pigs. Results showed that malic acid supplementation for 28 days increased oxidative fiber percentage of weaned piglets, accompanied by the increased aerobic oxidation in serum and longissimus thoracis (LT) muscle. Additionally, activities of total antioxidant capacity and glutathione peroxidase in serum were increased. Moreover, dietary malic acid supplementation during nursery period tended to increase pH24h and significantly decreased drip loss in LT muscle of finishing pigs. The content of total saturated fatty acid (SFA) and total monounsaturated fatty acid in LT muscle was significantly decreased, whereas the ratio of polyunsaturated fatty acid to SFA tended to increase. Together, dietary malic acid supplementation during nursery period can effectively increase antioxidant capacity and oxidative fibers percentage of weaned piglets, and further improve water holding capacity and nutritional values of pork in finishing pigs.

trans 10, cis 12, but Not cis 9, trans 11 Conjugated Linoleic Acid Isomer Enhances Exercise Endurance by Increasing Oxidative Skeletal Muscle Fiber Type via Toll-like Receptor 4 Signaling in Mice.

Conjugated linoleic acid (CLA) has been implicated in regulating muscle fiber. However, which isomer elicits this effect and the underlying mechanisms remain unclear. Here, male C57BL6/J mice and C2C12 cells were treated with two CLA isomers, and the exercise endurance, skeletal muscle fiber type, and involvement of Toll-like receptor 4 (TLR4) signaling were assessed. The results demonstrated that dietary t10, c12, but not c9, t11-CLA isomer enhanced exercise endurance of mice (from 115.88 ± 11.21 to 130.00 ± 15.84 min, P < 0.05) and promoted the formation of oxidative muscle fiber type of gastrocnemius muscle (from 0.15 ± 0.04 to 0.24 ± 0.05, P < 0.05). Consistently, t10, c12-CLA isomer increased the mRNA expression of oxidative muscle fiber type in C2C12 myotubes (from 1.00 ± 0.08 to 2.65 ± 1.77, P < 0.05). In addition, t10, c12-CLA isomer increased TLR4 signaling expression in skeletal muscle and C2C12 myotubes. More importantly, knockdown of TLR4 eliminated the t10, c12-CLA isomer-induced enhancement of exercise endurance in mice and elevation of oxidative muscle fiber type in C2C12 myotubes and gastrocnemius muscle. Together, these findings showed that t10, c12, but not c9, t11-CLA isomer enhances exercise endurance by increasing oxidative skeletal muscle fiber type via TLR4 signaling.

Naringin induces skeletal muscle fiber type transformation via AMPK/PGC-1α signaling pathway in mice and C2C12 myotubes.

A large number of studies have shown that polyphenols can regulate skeletal muscle fiber type transformation through AMPK signal. However, the effects and mechanism of naringin (a natural polyphenol) on muscle fiber type transformation still remains unclear. Thus, we hypothesized that naringin would induce the transformation of skeletal muscle fibers from type II to type I by AMPK signaling. C2C12 myotubes and BALB/c mice models were used to test this hypothesis. We found that naringin significantly increased the protein expression of slow myosin heavy chain (MyHC), myoglobin and troponin I type I slow skeletal (Troponin I-SS) and the activities of succinate dehydrogenase (SDH) and malate dehydrogenase (MDH), and significantly decreased fast MyHC protein expression and lactate dehydrogenase (LDH) activity, accompanied by the activation of AMPK and the activity of peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) in mice and C2C12 myotubes. Further inhibition of AMPK activity by compound C showed that the above effects were significantly inhibited in C2C12 myotubes. In conclusion, naringin promotes the transformation of skeletal muscle fibers from type II to type I through AMPK/PGC-1α signaling pathway, which not only enriches the nutritional and physiological functions of naringin, but also provides a theoretical basis for the regulation of muscle fiber type transformation by nutritional approaches.

Lauric Acid Accelerates Glycolytic Muscle Fiber Formation through TLR4 Signaling.

Lauric acid (LA), which is the primary fatty acid in coconut oil, was reported to have many metabolic benefits. TLR4 is a common receptor of lipopolysaccharides and involved mainly in inflammation responses. Here, we focused on the effects of LA on skeletal muscle fiber types and metabolism. We found that 200 µM LA treatment in C2C12 or dietary supplementation of 1% LA increased MHCIIb protein expression and the proportion of type IIb muscle fibers from 0.452 ± 0.0165 to 0.572 ± 0.0153, increasing the mRNA expression of genes involved in glycolysis, such as HK2 and LDH2 (from 1.00 ± 0.110 to 1.35 ± 0.0843 and from 1.00 ± 0.123 to 1.71 ± 0.302 in vivo, respectively), decreasing the catalytic activity of lactate dehydrogenase (LDH), and transforming lactic acid to pyruvic acid. Furthermore, LA activated TLR4 signaling, and TLR4 knockdown reversed the effect of LA on muscle fiber type and glycolysis. Thus, we inferred that LA promoted glycolytic fiber formation through TLR4 signaling.

Arginine promotes skeletal muscle fiber type transformation from fast-twitch to slow-twitch via Sirt1/AMPK pathway.

This study investigated the effect of arginine on skeletal muscle fiber type transformation in mice and in C2C12 myotubes. Our data showed that dietary supplementation of arginine in mice significantly up-regulated the slow myosin heavy chain (MyHC), troponin I-SS, sirtuin1 (Sirt1) and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) protein expressions, as well as significantly down-regulated the fast MyHC protein expression. In C2C12 myotubes, arginine significantly increased the protein level of slow MyHC and the number of slow MyHC-positive cells, as well as significantly decreased the protein level of fast MyHC and the number of fast MyHC-positive cells. We also showed that arginine increased the activities of succinic dehydrogenase and malate dehydrogenase and decreased the activity of lactate dehydrogenase in mice and in C2C12 myotubes. Here we found that AMP-activated protein kinase (AMPK) was activated by arginine in mice and in C2C12 myotubes. However, inhibition of AMPK activity by compound C significantly attenuated the effects of arginine on slow MyHC and fast MyHC expressions in C2C12 myotubes. Finally, we showed that inhibition of Sirt1 expression by EX527 attenuated arginine-induced increase in the protein levels of phospho-AMPK and slow MyHC, the mRNA level of nitric oxide synthase (NOS) and the contents of NOS and NO, as well as decrease in fast MyHC protein level. Together, our findings indicated that arginine promotes skeletal muscle fiber type switching from fast-twitch to slow-twitch via Sirt1/AMPK pathway.

Phytol Promotes the Formation of Slow-Twitch Muscle Fibers through PGC-1α/miRNA but Not Mitochondria Oxidation.

Phytol is a side chain of chlorophyll belonging to the side-chain double terpenoid. When animals consume food rich in chlorophyll, phytol can be broken down to phytanic acid after digestion. It was reported that feeding animals with different varieties and levels of forage could significant improve pH and marbling score of steer and lamb carcasses, but the internal mechanism for this is still not reported. The marbling score and pH of muscle was mainly determined by skeletal muscle fiber type, which is due to expression of different myosin heavy-chain (MHC) isoforms. Here, we provide evidence that phytol can indeed affect the diversity of muscle fiber types both in vitro and in vivo and demonstrate that phytol can increase the expression of MHC I (p < 0.05), likely by upgrading the expression of PPARδ, PGC-1α, and related miRNAs. This fiber-type transformation process may not be caused by activated mitochondrial metabolism but by the structural changes in muscle fiber types.

Creatine kinase as a marker of obesity in a multi-ethnic population.

OBJECTIVE: Creatine kinase (CK), the central regulatory enzyme of energy metabolism, is particularly high in type II skeletal muscle fibers, which are associated with insulin resistance and obesity. As resting plasma CK is mainly derived from skeletal muscle, we assessed whether plasma CK is associated with markers of obesity. METHODS: In this cross-sectional study, we analyzed a random sample of the multi-ethnic population of Amsterdam, the Netherlands, consisting of 1444 subjects aged 34-60 years. The primary outcome was the independent association between plasma CK after rest and waist circumference. Other outcomes included waist-to-hip ratio and body mass index. RESULTS: Mean waist circumference increased from the first through the third CK tertile, respectively 90.3 (SD 13.4), 93.2 (SD 14.3), and 94.4 (SD 13.3) cm (p < 0.001 for differences between tertiles). The increase in waist circumference was 8.91 (95% CI 5.35 to 12.47) cm per log CK increase after adjustment for age, sex, African ethnicity, educational level, physical activity and plasma creatinine. Similarly, CK was independently associated with waist-to-hip ratio and body mass index, with an increase of respectively 0.05 (95% CI 0.03 to 0.07) and 3.6 (95% CI 2.3 to 5.0) kg/m2 per log CK increase. CONCLUSIONS: Plasma CK is independently associated with measures of obesity in a multi-ethnic population. This is in line with the central role of type II skeletal muscle fibers in energy metabolism and obesity. Prospective studies should assess whether resting plasma CK could be an easy accessible marker of CK rich type II fiber predominance that helps identify individuals at risk for obesity.

Treadmill Slope Modulates Inflammation, Fiber Type Composition, Androgen, and Glucocorticoid Receptors in the Skeletal Muscle of Overtrained Mice.

Overtraining (OT) may be defined as an imbalance between excessive training and adequate recovery period. Recently, a downhill running-based overtraining (OTR/down) protocol induced the nonfunctional overreaching state, which is defined as a performance decrement that may be associated with psychological and hormonal disruptions and promoted intramuscular and systemic inflammation. To discriminate the eccentric contraction effects on interleukin 1beta (IL-1ß), IL-6, IL-10, IL-15, and SOCS-3, we compared the release of these cytokines in OTR/down with other two OT protocols with the same external load (i.e., the product between training intensity and volume), but performed in uphill (OTR/up) and without inclination (OTR). Also, we evaluated the effects of these OT models on the muscle morphology and fiber type composition, serum levels of fatigue markers and corticosterone, as well as androgen receptor (AR) and glucocorticoid receptor (GR) expressions. For extensor digitorum longus (EDL), OTR/down and OTR groups increased the cytokines and exhibited micro-injuries with polymorphonuclear infiltration. While OTR/down group increased the cytokines in soleus muscle, OTR/up group only increased IL-6. All OT groups presented micro-injuries with polymorphonuclear infiltration. In serum, while OTR/down and OTR/up protocols increased IL-1ß, IL-6, and tumor necrosis factor alpha, OTR group increased IL-1ß, IL-6, IL-15, and corticosterone. The type II fibers in EDL and soleus, total and phosphorylated AR levels in soleus, and total GR levels in EDL and soleus were differentially modulated by the OT protocols. In summary, the proinflammatory cytokines were more sensitive for OTR/down than for OTR/up and OTR. Also, the specific treadmill inclination of each OT model influenced most of the other evaluated parameters.