Exercise Training Reduces Insulin Resistance and Upregulates the mTOR/p70S6k Pathway in Cardiac Muscle of Diet-Induced Obesity Rats

Obesity and insulin resistance are rapidly expanding public health problems. These disturbances are related to many diseases, including heart pathology. Acting through the Akt/mTOR pathway, insulin has numerous and important physiological functions, such as the induction of growth and survival of many cell types and cardiac hypertrophy. However, obesity and insulin resistance can alter mTOR/p70S6k. Exercise training is known to induce this pathway, but never in the heart of diet-induced obesity subjects. To evaluate the effect of exercise training on mTOR/p70S6k in the heart of obese Wistar rats, we analyzed the effects of 12 weeks of swimming on obese rats, induced by a high-fat diet. Exercise training reduced epididymal fat, fasting serum insulin and plasma glucose disappearance. Western blot analyses showed that exercise training increased the ability of insulin to phosphorylate intracellular molecules such as Akt (2.3-fold) and Foxo1 (1.7-fold). Moreover, reduced activities and expressions of proteins, induced by the high-fat diet in rats, such as phospho-JNK (1.9-fold), NF-kB (1.6-fold) and PTP-1B (1.5-fold), were observed. Finally, exercise training increased the activities of the transduction pathways of insulin-dependent protein synthesis, as shown by increases in Raptor phosphorylation (1.7-fold), p70S6k phosphorylation (1.9-fold), and 4E-BP1 phosphorylation (1.4-fold) and a reduction in atrogin-1 expression (2.1-fold). Results demonstrate a pivotal regulatory role of exercise training on the Akt/ mTOR pathway, in turn, promoting protein synthesis and antagonizing protein degradation. J. Cell. Physiol. 226: 666-674, 2011. (C) 2010 Wiley-Liss, Inc.

Alterations in myocardial collagen content affect rat papillary muscle function

We investigated the influence of myocardial collagen volume fraction (CVF, %) and hydroxyproline concentration (mu g/mg) on rat papillary muscle function. Collagen excess was obtained in 10 rats with unilateral renal ischemia for 5 wk followed by 3-wk treatment with ramipril (20 mg . kg(-1) . day(-1)) (RHTR rats; CVF = 3.83 +/- 0.80, hydroxyproline = 3.79 +/- 0.50). Collagen degradation was induced by double infusion of oxidized glutathione (GSSG rats; CVF 5 2.45 +/- 0.52, hydroxyproline = 2.85 +/- 0.18). Nine untreated rats were used as controls (CFV = 3.04 +/- 0.58, hydroxyproline = 3.21 +/- 0.30). Active stiffness (AS; g . cm(-2) . %L-max(-1)) and myocyte cross-sectional area (MA; mu m(2)) were increased in the GSSG rats compared with controls [AS 5.86 vs. 3.96 (P< 0.05); MA 363 +/- 59 vs. 305 +/- 28 (P< 0.05)]. In GSSG and RHTR groups the passive tension-length curves were shifted downwards, indicating decreased passive stiffness, and upwards, indicating increased passive stiffness, respectively. Decreased collagen content induced by GSSG is related to myocyte hypertrophy, decreased passive stiffness, and increased AS, and increased collagen concentration causes myocardial diastolic dysfunction with no effect on systolic function.

The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

We have investigated the effects of L-arginine, D-arginine and L-lysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM) significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM) in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM) failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P>0.05). In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, NG-nitro L-arginine methyl ester (L-NAME; 50 µM). Thus, at very high concentrations, arginine exhibit a non-competitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect.

Partial molecular characterization of the Nile tilapia (Oreochromis niloticus) alpha-cardiac muscle actin gene and its relationship to actin isoforms of other fish species

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparative mechanical study of isolated papillary muscle from Wistar-Kyoto and Wistar rats

Isolated papillary muscles have often been used in myocardial mechanical function studies. The objective of the present study was to compare the mechanical function of papillary muscle isolated from left ventricle between Wistar (W) and Wistar-Kyoto (WKY) rats of different ages (1, 3, 6 and 12 months), in order to examine whether there is a difference in intrinsic mechanical properties of muscle between the two rat strains. Muscles were perfused with Krebs-Henseleit solution at 28°C and studied isometrically and isotonically at a stimulation rate of 0.2 Hz. The W and WKY showed statistically significant differences during both isometric and isotonic contractions. During isometric contraction? (l) the peak developed tension (DT) and + dT/dt were lower in WKY rats in the 1 mo groups, (2) the resting tension (RT) was greater in WKY at 3, 6 and 12 mo. (3) time to peak tension (TPT) was greater in WKY at 3 and 12 mo, (4) time for tension to fall from peak to 50% of peak tension (RT 1/2) was greater in WKY at 3 mo and (5) - dT/dt was lower in WKY at 1 and 3 mo. During isotonic contraction, (1) the peak shortening (PS) and -dL/dt were lower in WKY at 12 mo, (2) the time to peak shortening (TPS) was greater in WKY at 3 and 12 mo; (3) + dL/dt was lower in WKY at 3, 6, and 12 mo and (4) the relative variation of length (Lmax-PS)/Lmax was greater in WKY at 6 and 12 mo. These data showed a difference in mechanical behaviour of the papillary muscle between Wistar and Wistar-Kyoto rats of different age.

Effects of olive oil and its minor constituents on serum lipids, oxidative stress, and energy metabolism in cardiac muscle

Recent lines of evidence suggest that the beneficial effects of olive oil are not only related to its high content of oleic acid, but also to the antioxidant potential of its polyphenols. The aim of this work was determine the effects of olive oil and its components, oleic acid and the polyphenol dihydroxyphenylethanol (DPE), on serum lipids, oxidative stress, and energy metabolism on cardiac tissue. Twenty four male Wistar rats, 200 g, were divided into the following 4 groups (n = 6): control (C), OO group that received extra-virgin olive oil (7.5 mL/kg), OA group was treated with oleic acid (3.45 mL/kg), and the DPE group that received the polyphenol DPE (7.5 mg/kg). These components were administered by gavage over 30 days, twice a week. All animals were provided with food and water ad libitum The results show that olive oil was more effective than its isolated components in improving lipid profile, elevating high-density lipoprotein, and diminishing low-density lipoprotein cholesterol concentrations. Olive oil induced decreased antioxidant Mn-superoxide dismutase activity and diminished protein carbonyl concentration, indicating that olive oil may exert direct antioxidant effect on myocardium. DPE, considered as potential antioxidant, induced elevated aerobic metabolism, triacylglycerols, and lipid hydroperoxides concentrations in cardiac muscle, indicating that long-term intake of this polyphenol may induce its undesirable pro-oxidant activity on myocardium. © 2006 NRC Canada.

Isokinetic eccentric resistance training prevents loss in mechanical muscle function after running

The aim of the study was to verify whether 8 weeks of resistance training employing maximal isokinetic eccentric (IERT) knee extensor actions would reduce the acute force loss observed after high-intensity treadmill running exercise. It was hypothesized that specific IERT would induce protective effects against muscle fatigue and ultrastructural damages, preventing or reducing the loss in mechanical muscle function after running. Subjects were tested before and after IERT protocol for maximal isometric, concentric and eccentric isokinetic knee extensor strength (60 and 180 s-1). In a second session, subjects performed treadmill running (~35 min) and the previously mentioned measurements were repeated immediately after running. Subsequently, subjects were randomized to training (n = 12) consisting of 24 sessions of maximal IERT knee extensors actions at 180 s-1, or served as controls (n = 8). The effects of acute running-induced fatigue and training on isokinetic and isometric peak torque, and rate of force development (RFD) were investigated. Before IERT, running-induced eccentric torque loss at 180 s-1 was -8 %, and RFD loss was -11 %. Longitudinal IERT led to reduced or absent acute running-induced losses in maximal IERT torque at 180 s-1 (+2 %), being significantly reduced compared to before IERT (p < 0.05), however, RFD loss remained at -11 % (p > 0.05). In conclusion, IERT yields a reduced strength loss after high-intensity running workouts, which may suggest a protective effect against fatigue and/or morphological damages. However, IERT may not avoid reductions in explosive muscle actions. In turn, this may allow more intense training sessions to be performed, facilitating the adaptive response to running training. © 2013 Springer-Verlag Berlin Heidelberg.

Cardiomyopathy and cell therapy: ejection fraction improvement and cardiac muscle mass increasing, after a year of bone marrow stem cells transplantation, by magnetic resonance image

The idiopathic dilated cardiomyopathy (IDC) is one of the major public health problems in the western world. Patients with IDC in functional class IV (New York Health Association - NYHA), even after therapeutic optimization, have high mortality. Stem cell therapy has emerged as a potential therapeutic option for cell death-related heart diseases and several positive effects were assigned to cell therapy in cardiomyopathy. The aim of this study was identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy patients (IDC) who were treated by transplantation of autologous bone marrow mononuclear cells (BMMC). Intracoronary injections of autologous BMMC were performed in eight patients with severe ventricle dysfunction (mean of left ventricle ejection fraction – LEVF=20.03%), cardiac mass muscle around 156.2 g and NYHA between III and IV grades, other 8 IDC patients received placebo. The IDCs were followed - up for one and two years, by magnetic resonance imaging (MRI). The results after one year showed significant improvement in LVEF (mean=181.4) and muscle mass increasing (mean=181.4 g), after two years the LVEF continued improving, reaching a mean of 32.69% and the cardiac muscle mass kept stable (mean=179.4 g). Excepted for one patient, all the other had improvement in the NYHA functional class. The placebo group did not show any improvement. We believe that BMMC implant may be a beneficial therapeutic option for IDC patients.

Effect of vitamin D supplementation alone on muscle function in postmenopausal women: a randomized, double-blind, placebo-controlled clinical trial

The present study investigates the effects of vitamin D on muscle function in postmenopausal women. It has been shown that vitamin D supplementation in postmenopausal women with hypovitaminosis D provides significant protective factor against sarcopenia, with significant increases in muscle strength and control of progressive loss of lean mass. We aimed to evaluate the effect of supplementation of vitamin D (VITD) alone on muscle function in younger postmenopausal women. In this double-blind, placebo-controlled clinical trial, 160 Brazilian postmenopausal women were randomized into two groups: VITD group consisting of patients receiving vitamin D3 1000 IU/day orally (n = 80) or placebo group (n = 80). Women with amenorrhea for more than 12 months and age 50-65 years, with a history of falls (previous 12 months), were included. The intervention time was 9 months, with assessments at two points, start and end. Lean mass was estimated by total-body dual-energy X-ray absorptiometry (DXA) and muscle strength by handgrip strength and chair rising test. The plasma concentrations of 25-hydroxyvitamin D [25(OH)D] were measured by high-performance liquid chromatography (HPLC). Statistical analysis was by intention to treat (ITT), using ANOVA, Student's t test, and Tukey's test. After 9 months, average values of 25(OH)D increased from 15.0 ± 7.5 to 27.5 ± 10.4 ng/ml (+45.4 %) in the VITD group and decreased from 16.9 ± 6.7 to 13.8 ± 6.0 ng/ml (-18.5 %) in the placebo group (p < 0.001). In the VITD group, there was significant increase in muscle strength (+25.3 %) of the lower limbs by chair rising test (p = 0.036). In women in the placebo group, there was considerable loss (-6.8 %) in the lean mass (p = 0.030). The supplementation of vitamin D alone in postmenopausal women provided significant protective factor against the occurrence of sarcopenia, with significant increases in muscle strength and control of progressive loss of lean mass.

Upper Brachial Plexus Injuries: Grafts vs Ulnar Fascicle Transfer to Restore Biceps Muscle Function

BACKGROUND: Nerve transfers or graft repairs in upper brachial plexus palsies are 2 available options for elbow flexion recovery. OBJECTIVE: To assess outcomes of biceps muscle strength when treated either by grafts or nerve transfer. METHODS: A standard supraclavicular approach was performed in all patients. When roots were available, grafts were used directed to proximal targets. Otherwise, a distal ulnar nerve fascicle was transferred to the biceps branch. Elbow flexion strength was measured with a dynamometer, and an index comparing the healthy arm and the operated-on side was developed. Statistical analysis to compare both techniques was performed. RESULTS: Thirty-five patients (34 men) were included in this series. Mean age was 28.7 years (standard deviation, 8.7). Twenty-two patients (62.8%) presented with a C5-C6 injury, whereas 13 patients (37.2%) had a C5-C6-C7 lesion. Seventeen patients received reconstruction with grafts, and 18 patients were treated with a nerve transfer from the ulnar nerve to the biceps. The trauma to surgery interval (mean, 7.6 months in both groups), strength in the healthy arm, and follow-up duration were not statistically different. On the British Medical Research Council muscle strength scale, 8 of 17 (47%) patients with a graft achieved >= M3 biceps flexion postoperatively, vs 16 of 18 (88%) post nerve transfers (P = .024). This difference persisted when a muscle strength index assessing improvement relative to the healthy limb was used (P = .031). CONCLUSION: The results obtained from ulnar nerve fascicle transfer to the biceps branch were superior to those achieved through reconstruction with grafts.

Is the History of Falls an Indicative of Greater Decline in Quadriceps Muscle Function and Postural Sway?

To evaluate whether a history of falls is directly related to the quadriceps muscular function and body sway, 26 elderly women were divided on the basis of the presence or absence of a history of falls. Evaluation of muscular power and anteroposterior and mediolateral displacements of center of pressure during consecutive stand and sit 5 times were performed. Fallers exhibited higher mediolateral displacement than nonfallers. No differences were observed for quadriceps power and for sit-to-stand time between groups (P<.05). The fall history was not related to the quadriceps muscular function or to the anteroposterior displacement during sit to stand.

Pseudomyotonia, a muscle function disorder associated with an inherited ATP2A1 (SERCA1) defect in a Dutch Improved Red and White cross-breed calf

A Dutch Improved Red and White cross-breed heifer calf was evaluated for a muscular disorder resulting in exercise induced muscle stiffness. Clinical findings included generalized exercise-induced muscle spasms with normal response to muscle percussion. Electromyography showed no myotonic discharges, thus ruling out myotonia. Whereas histological examination of muscle tissue was unremarkable, Ca(2+)-ATPase activity of sarcoplasmatic reticulum membranes (SERCA1) was markedly decreased compared to control animals. Mutation analysis revealed the presence of a missense mutation in the ATP2A1 gene encoding the SERCA1 protein (p.Arg559Cys). The present case presents similarities to human Brody's disease, but also to pseudomyotonia and congenital muscular dystonia previously described in different cattle breeds.