Tibialis Anterior Muscle Mass Research Articles

The effect of ladder-climbing exercise on atrophy/hypertrophy-related myokine expression in middle-aged male Wistar rats.

We investigated the change in myokine expression related to hypertrophy (IL-4, IL-6, IL-10) and atrophy (TNF-α, NFκB, IL-1β) in middle-aged rats after resistance exercise with ladder climbing. 50- and 10-week-old male Wistar rats were randomly assigned to two groups: the sedentary and exercise groups. The exercise groups underwent a ladder-climbing exercise for 8 weeks. While the tibialis anterior muscle mass in the young group significantly increased after the ladder-climbing exercise, the middle-aged group did not show any changes after undergoing the same exercise. To understand the molecular mechanism causing this difference, we analyzed the change in hypertrophy- and atrophy-related myokine levels from the tibialis anterior muscle. After 8 weeks of ladder-climbing exercise, the IL-4 and IL-10 protein levels did not change. However, the IL-6 level significantly increased after exercise training, but the amount of increase in the young training group was higher than in the middle-aged training group. IL-1β and TNF-α as well as NFκB protein levels were significantly higher in the middle-aged group than in the young group. Except for TNF-α, exercise training did not affect IL-1β and NFκB protein levels. The TNF-α level significantly decreased in the middle-aged exercise training group. AMPK and PGC-1α levels also significantly increased after exercise training, but there was no difference between age-related groups. Therefore, 8-week high-intensity exercise training using ladder climbing downregulates the skeletal muscle production of myokine involved in atrophy and upregulates hypertrophic myokine. However, the extent of these responses was lower in the middle-aged than young group.

STAT3 Regulation In Cachectic Skeletal Muscle After Repeated Eccentric Contractions

Introduction The cachectic muscle's response to multiple bouts of eccentric contractions (ECC) has not been examined. We examined if 2 weeks of repeated ECC training could alter STAT3 regulation in cachectic muscle. Methods Male C57BL/6 (B6; N=9) and ApcMin/+ mice were subjected to 7 bouts of high-frequency electrical stimulation (100 Hz, 6-12V, 10 sets of 6 repetitions) over 2 weeks. The left tibialis anterior (TA) muscle performed ECC while the right TA served as an intra-animal control. ApcMin/+ mice were stratified into mild (7%; N=5) and severe (16% loss; N=4) cachexia based on the percentage of body weight loss at the end of the study. Results ApcMin/+ mice had smaller control TA muscle mass (-26%; P<.01) and type IIA and IIB myofiber cross-sectional area (CSA) compared to B6 mice. Cachexia increased control TA muscle STAT3 phosphorylation (9-fold; P<.05), p42/44 MAPK phosphorylation (8-fold; P<.05), and Atrogin-1 protein expression (9-fold; P<.05). Independent of cachexia ECC increased TA muscle mass and type IIA and IIB myofiber CSA. ECC had no effect on TA muscle STAT3 phosphorylation in mildly cachectic mice, but there was a 30% reduction (P<.01) in severely cachectic mice. ECC had no effect on muscle p42/p44 MAPK phosphorylation in ApcMin/+ mice. The induction of Atrogin-1 protein expression was attenuated 31% (P<.01) by ECC in severely cachectic mice. Conclusion These results suggest that repeated bouts of ECC can alter cachexia-induced muscle signaling. The contraction-induced regulation of STAT3 signaling during cachexia progression warrants further investigation. Supported by NIH/NCI R01CA121249 to JAC.

Extracellular signal-regulated kinase-mammalian target of rapamycin signaling and forkhead-box transcription factor 3a phosphorylation are involved in testosterone's effect on severe burn injury in a rat model.

Testosterone and androgen receptor agonists have been known for a long time to prevent or reverse muscle wasting in burn injury patients, but the exact molecular mechanisms are not clear. To investigate the underlying molecular mechanisms of testosterone in severely burned rats. Severe burn injuries were induced by immersing the back of the rat in 100 °C water for 12 s. Rats were treated for 14 days with vehicle (burn group) or a physiological replacement dose of testosterone (B + T group) immediately after injury. Gene and protein expressions were assessed by real-time polymerase chain reaction and Western blot. Testosterone improved glucose metabolism, reduced body weight loss, and attenuated tibialis anterior muscle mass loss and muscle protein breakdown. In rat tibialis anterior muscle, testosterone positively regulated the insulin-sensitive glucose transporters Glut3 and Glut4 genes and glycogen synthase 1 protein. These changes would be expected to improve glucose metabolism and nutrient availability in skeletal muscle. Administration of testosterone negatively regulated atrogin 1 (Fbxo32) by increasing total and phosphorylated Foxo3a (forkhead-box transcription factor 3a) levels and positively regulated the expression of the mammalian target of rapamycin (mTOR) and its downstream proteins p70S6 and S6 through mTOR-extracellular signal-regulated kinase phosphorylation. RESULTS suggested that testosterone might regulate skeletal muscle glucose and protein metabolism following burn injury in part by affecting extracellular signal-regulated kinase-mTOR signaling and Foxo3a levels.

Monocarboxylate transporter expression at the onset of skeletal muscle regeneration

Monocarboxylate transporters (MCTs) are involved in lactate transport across the cell membrane and this has important implications for energetic efficiency of skeletal muscle. MCT expression is affected by mechanical overload, chronic electrical stimuli, and voluntary wheel running. However, the cellular regulation of MCT protein expression at the onset of skeletal muscle regeneration is unknown.PURPOSETo determine protein and gene expression of MCTs at the onset of skeletal muscle regeneration. Male C57/BL6 (12 weeks old) mice were randomly assigned to a control (uninjured) or bupivacaine (injured) group. Bupivacaine was injected into the tibialis anterior (TA) of the injured group and phosphate buffered saline (PBS) was injected into the TA of the uninjured group. The TA was extracted 3 days post‐bupivacaine injection. A 12% decrease in TA muscle mass to tibia length (2.43 ± 0.12 mg/mm vs. 2.14 ± 0.19 mg/mm, p &lt; 0.02) was observed. IGF‐1 and myoD gene expression increased 5.0‐fold (p &lt; 0.05) and 3.5‐fold (p &lt; 0.05), respectively during regeneration. MCT1 protein decreased 32% (p &lt; 0.03); however, gene expression was not altered. There was no difference in MCT4 protein or gene expression. CD147 and PKCθ protein increased 64% (p &lt; 0.03) and 79% (p &lt; 0.02), respectively. In conclusion, at the onset of skeletal muscle regeneration MCT1 protein is decreased and this appears to be regulated post‐transcriptionally.

Melatonin and/or therapeutic exercise induces autophagy‐mediated muscles remodeling in collagenase‐induced osteoarthritic rats

Osteoarthritis (OA) is characterized by progressive degeneration of arthritic cartilage, subsequent joint narrowing, and abnormal gait. The purpose of this study is to determine the effects of melatonin and/or exercise on the muscle remodeling and functional gait in collagenase‐induced OA rats. Melatonin (MT) injection was performed twice/day subcutaneously. The treadmill exercise (Ex) was conducted for 1‐hr/day at the frequency of 5 days/week. As results, body weight was significantly reduced by melatonin and/or exercise (P&lt;.05), whereas no significance was shown in gastrocnemius as well as tibialis anterior muscle mass in OA+MT and OA+MT+Ex group at day 28. MAFbx, ubiquitin E3 ligase, was increased in medial gastrocnemius muscle in OA+MT+Ex group at day 7 (P&lt;.05). Intervention also induced an upregulation of autophagic molecules, LC3 and BECN1 (P&lt;.05). At day 28, the relative distribution of MHC1b was significantly increased in gastrocnemius muscle of OA+MT and OA+MT+Ex groups (P&lt;.05). Sarcomeric Nebulin was increased by melatonin and/or treadmill exercise at day 28 (P&lt;.05). Furthermore, as a result of footprint, intervention increased feet contact area. Taken together, melatonin and/or exercise activated autophagic machinery inducing muscle structural remodeling in collagenase‐induced OA rats.

Increased Expression of Wild-Type or a Centronuclear Myopathy Mutant of Dynamin 2 in Skeletal Muscle of Adult Mice Leads to Structural Defects and Muscle Weakness

Dynamin 2 (DNM2) is a large GTPase implicated in many cellular functions, including cytoskeleton regulation and endocytosis. Although ubiquitously expressed, DNM2 was found mutated in two genetic disorders affecting different tissues: autosomal dominant centronuclear myopathy (ADCNM; skeletal muscle) and peripheral Charcot-Marie-Tooth neuropathy (peripheral nerve). To gain insight into the function of DNM2 in skeletal muscle and the pathological mechanisms leading to ADCNM, we introduced wild-type DNM2 (WT-DNM2) or R465W DNM2 (RW-DNM2), the most common ADCNM mutation, into adult wild-type mouse skeletal muscle by intramuscular adeno-associated virus injections. We detected altered localization of RW-DNM2 in mouse muscle. Several ADCNM features were present in RW-DNM2 mice: fiber atrophy, nuclear mislocalization, and altered mitochondrial staining, with a corresponding reduction in specific maximal muscle force. The sarcomere and triad structures were also altered. We report similar findings in muscle biopsy specimens from an ADCNM patient with the R465W mutation. In addition, expression of wild-type DNM2 induced some muscle defects, albeit to a lesser extent than RW-DNM2, suggesting that the R465W mutation has enhanced activity in vivo. In conclusion, we show the RW-DNM2 mutation acts in a dominant manner to cause ADCNM in adult muscle, and the disease arises from a primary defect in skeletal muscle rather than secondary to peripheral nerve involvement. Therefore, DNM2 plays important roles in the maintenance of adult muscle fibers.

Dietary zinc mediates inflammation and protects against wasting and metabolic derangement caused by sustained cigarette smoke exposure in mice

In mouse asthma models, inflammation can be modulated by zinc (Zn). Given that appetite loss, muscle wasting and poor nutrition are features of chronic obstructive pulmonary disease (COPD) and that poor dietary Zn intake is in itself accompanied by growth retardation and appetite loss, we hypothesised that dietary Zn limitation would not only worsen airway inflammation but also exaggerate metabolic effects of cigarette smoke (CS) exposure in mice. Conversely, Zn supplementation would lessen inflammation. Mice were exposed to CS [2× 2RF, 3×/day; 15 min/cigarette] and fed diets containing 2, 20 or 140 mg/kg Zn ad libitum. Airway cells were collected by bronchoalveolar lavage (BAL). Plasma Zn was measured by fluorometric assay. Inflammatory, metabolic and Zn transport markers were measured by real-time RT-PCR. Mice fed low Zn diets had less plasma labile zinc (0-0.18 μM) than mice fed moderate (0.61-0.98 μM) or high (0.77-1.1 μM) Zn diets (SDs 0.1-0.4, n = 8-10). Smoke exposure increased plasma and BAL labile Zn (1.5-2.5 fold, P < 0.001), bronchoalveolar macrophages (2.0 fold, P < 0.0001) and MT-1 (1.5 fold), MIP-2 (2.3 fold) and MMP-12 (3.5 fold) mRNA. Zn supplementation reduced alveolar macrophage numbers by 62 and 52% in sham and smoke-exposed mice, respectively (Zn effect: P = 0.011). Gastrocnemius, soleus and tibialis anterior muscle mass were affected by both smoke and dietary Zn in the order of 3-7%. The 50-60% reduction in alveolar macrophages in Zn-supplemented mice supports our evolving hypothesis that Zn is an important anti-inflammatory mediator of airway inflammation. Restoring airway Zn levels through dietary supplementation may lessen the severity of lung inflammation when Zn intake is low.

Leptin and Obesity Alter Expression of Myostatin and its Receptor ActRIIb in Mouse Skeletal Muscle

Myostatin is an anti-growth factor expressed in skeletal muscle that has profound effects on the mass of both tissues. PURPOSE. In the present study, we used quantitative real-time polymerase chain reaction (QRT-PCR) to determine mRNA levels for myostatin (MSTN) and its primary receptor activin RIIb (ActRIIb) in the tibialis anterior (TA) and soleus (SOL) skeletal muscles of genetically obese leptin-deficient mice, leptin-deficient mice injected with recombinant leptin for two weeks, and in dietarily obese mice. RESULTS. TA muscle mass was significantly lower in leptin-deficient ob/ob mice but SOL mass was not significantly different between ob/ob mice and wild type C57 mice. Similarly, MSTN mRNA levels were significantly increased in TA but not the SOL of ob/ob mice compared to nonobese control mice. Interestingly, leptin injection significantly decreased MSTN mRNA levels in the TA of ob/ob mice despite the fact that it had no significant affect on TA muscle mass. ActRIIb mRNA levels were unchanged by either leptin deficiency or leptin replacement in either TA or SOL. Feeding mice a high fat diet (HFD) increased body mass and fat mass at 1 week, 1 month, and 3 months compared to age-matched littermate mice fed a normal diet (ND). TA mass was significantly increased after 1 week in HFD mice compared to ND mice but was not significantly different at 1 month or 3 months on a HFD. Soleus mass was unchanged at any timepoint. Interestingly, MSTN and ActRIIb mRNA levels in the TA were unchanged at 1 week, significantly increased at 1 month, and not significantly different at 3 months in HFD mice compared to ND mice. In the soleus MSTN mRNA levels were unchanged or slightly decreased in HFD mice but ActRIIb mRNA levels were significantly increased at 1 month on a high fat diet compared to ND mice. CONCLUSIONS: In summary, both muscle mass and MSTN expression are altered by obesity, but the alterations (1) differ between genetically obese and dietarily obese mice; (2) differ between muscle types (TA vs. SOL), and (3) are not temporally associated. Thus MSTN expression appears to be regulated by increased fat/caloric intake, and may play a role in the regulation of muscle mass or metabolism during the obese state.

Two Experimental Strategies to Restore Muscle Mass in Adult Rats Following Spinal Cord Injury

Spinal cord injury decreases muscle mass and is associated with myofiber type trans formations in skeletal muscles. The present study evaluated the potential of motor- assisted cycling exercise or transplantation of fetal spinal cord tissue into the lesion cavity to inhibit or minimize these changes in skeletal muscles of 27 adult female Sprague-Dawley rats. Soleus (SO) and tibialis anterior (TA) muscles were studied 30 to 32 days after injury/intervention in the following groups: uninjured control ani mals (Con); spinal cord injured only (Tx); Tx with a 4-week exercise program con sisting of five weekly 60-minute sessions of cycling exercise initiated 5 days after in jury (TxEx); and Tx with fetal spinal cord tissue transplanted into the lesion cavity at the time of injury (TxTp). SO and TA muscle to body weight ratios were reduced significantly in the Tx group (24-30% decrease vs Con, p &lt; 0.05) but were maintained with regular cycling exercise (6-8% decrease vs Con, no significant difference). The transplant had a beneficial effect on TA muscle mass (16% decrease vs Con, no sig nificant difference) but was not effective in limiting the effects of Tx on SO muscle mass. Immunohistochemistry and Northern analysis of TA and SO muscles revealed a Tx-induced reduction in myofiber cross sectional area (22% and 33% vs Con re spectively, p &lt; 0.05) as well as a conversion in myosin heavy chain (MyHC) expres sion toward faster MyHC isoforms. Moreover, one month after injury, there was an increase in myofibers expressing more than one MyHC. mRNA encoding MyoD, a muscle-specific transcription factor, was increased in SO muscles suggesting that it may be involved in the long-term adaptations following spinal cord transection. Although cycling exercise was effective in preventing the decrease in myofiber area in both TA and SO, it did not inhibit the transformations of myofiber type. TA myofiber area was maintained in transplant recipients, however, this treatment was without conse quence on the size of SO myofibers. These results suggest that some of the normally observed spinal cord injury-induced skeletal muscle adaptations are minimized after one month of cycling exercise or fetal spinal cord tissue transplants. Key Words: Myosin heavy chain—Exercise—MyoD—Fetal tissue transplantation—Fiber types.