White Vastus Lateralis Muscle Research Articles

The Effects of Resistance Exercise Training on Skeletal Muscle Metabolism and Insulin Resistance Development in Female Rodents with Type 1 Diabetes.

The etiology of insulin resistance (IR) development in type 1 diabetes mellitus (T1DM) remains unclear; however, impaired skeletal muscle metabolism may play a role. While IR development has been established in male T1DM rodents, female rodents have yet to be examined in this context. Resistance exercise training (RT) has been shown to improve IR and is associated with a lower risk of hypoglycemia onset in T1DM compared to aerobic exercise. The purpose of this study was to investigate the effects of RT on IR development in female T1DM rodents. Forty Sprague Dawley eight-week-old female rats were divided into four groups: control sedentary (CS; n = 10), control trained (CT; n = 10), T1DM sedentary (DS; n = 10), and T1DM trained (DT; n = 10). Multiple low-dose streptozotocin injections were used to induce T1DM. Blood glucose levels were maintained in the 4-9 mmol/l range with intensive insulin therapy. CT and DT underwent weighted ladder climbing 5 days/week for six weeks. Intravenous glucose tolerance tests (IVGTT) were conducted on all animals following the six-week period. Results demonstrate that DS animals exhibited significantly increased weekly blood glucose measures compared to all groups including DT (p < 0.0001), despite similar insulin dosage levels. This was concomitant with a significant increase in insulin-adjusted area under the curve following IVGTT in DS (p < 0.05), indicative of a reduction in insulin sensitivity. Both DT and DS exhibited greater serum insulin concentrations compared to CT and CS (p < 0.05). DS animals also exhibited significantly greater glycogen content in white gastrocnemius muscle compared to CS and DT (p < 0.05), whereas DT and DS animals exhibited greater p-Akt: Akt ratio in the white vastus lateralis muscle and citrate synthase activity in the red vastus lateralis muscle compared to CS and CT (p < 0.05). These results indicate that female rodents with T1DM develop poor glycemic control and IR which can be attenuated with RT, possibly related to differences in intramyocellular glycogen content.

Nrf2 regulates skeletal muscle mass and function in a mouse model of experimental autoimmune myositis

Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune disorders affecting skeletal muscle, which are characterized by loss of muscle mass and function. We have previously demonstrated that experimental autoimmune myositis (EAM) mice, a widely used animal model for IIMs, induced intrinsic contractile dysfunction, which is associated with increased oxidative stress. Here, we investigated the role of Nrf2, the master regulator of antioxidant gene transcription, in muscle mass and function from EAM mice. EAM was induced in muscle-specific Nrf2 knockout (Nrf2 mKO) and wild-type littermates (WT) mice by immunization with three injections of myosin emulsified in complete Freund's adjuvant. At 4 weeks after the first immunization, a grip strength test was performed using a grip strength meter. After that, mice were sacrificed by cervical dislocation under isoflurane anesthesia and harvested oxidative soleus, plantaris, tibialis anterior, gastrocnemius with mixed fiber types, glycolytic extensor digitorum longus, and white vastus lateralis muscles. Nrf2 mKO mice tended to attenuate EAM-induced decrease of muscle force. Nrf2 mKO mice significantly attenuates EAM-induced decrease of muscle weight in the glycolytic extensor digitorum longus, but not in the oxidative muscle. These results suggested that loss of Nrf2 help preserve muscle mass and function in EAM mice, which may be attributed to the mechanisms other than regulation of antioxidant defense by Nrf2.

Lack of muscle p62/SQSTM1 protects against high fat diet‐induced muscle wasting

Skeletal muscle atrophy is a hallmark of aging and several debilitating diseases (e.g., cancer, congestive heart failure, and type II diabetes) that contribute to morbidity and mortality. Oxidative stress plays an important role in skeletal muscle atrophy in these situations. Therefore, increased antioxidants expression could be a potentially protective measure against oxidative stress and skeletal muscle atrophy. We recently reported that p62/SQSTM1 expression in skeletal muscle contributes to control exercise training‐induced antioxidant enzymes expression with established p62 muscle‐specific knockout mice (p62mKO). However, the role of muscle p62 expression in type II diabetes induced‐muscle wasting was still not understood. Aim of this study was to elucidate the role of muscle p62 in type II diabetes induced‐muscle atrophy. p62mKO and their wild‐type littermates (WT) were fed normal chow (NC) or 45% fat diet (HFD) for 10 weeks. Body weight and food intake were measured every week. Glucose or insulin tolerance test were conducted at the 8 weeks. A grip strength test was performed at the end of HFD feeding. At 10 weeks, mice were sacrificed and harvested soleus (SO), gastrocnemius (GA), tibialis anterior (TA), extensor digitorum longus (EDL), and white vastus lateralis (WV) muscle. These muscles were measured weight and used for evaluation of protein expression. Muscle weight was measured by semi‐micro analytical balances and normalized by tibia length. Carbonylated protein was measures by western blot. Body weight, food intake, glucose and insulin tolerance ability, and grip strength were not significantly different between HFD fed p62mKO (p62mKO‐HFD) mice and HFD fed WT (WT‐HFD) mice. p62mKO‐HFD mice significantly attenuated loss of GA and EDL muscle weight. Carbonylated protein expression in p62mKO‐HFD mice was significantly lower than WT‐HFD mice. These results suggested that lack of muscle p62 protects against high fat diet‐induced muscle wasting via an antioxidants synthesis‐independent pathway.Support or Funding InformationThis study was supported by Grant‐in‐Aid for Research Activity Start‐Up (25882036), Grant‐in‐Aid for Scientific Research (B) (15H03080), Grant‐in‐Aid for Scientific Research (B) (18H03153), The Nakatomi Foundation, and The Uehara Memorial Foundation (to M.O.).

Muscle contractile activity regulates SDF‐1α/CXCL12 expression in skeletal muscle

ObjectiveExercise training induces an increase in capillarity density in skeletal muscle. Chemokines, a family of 8‐ to 10‐kDa chemotactic cytokines, provide signals that regulate cell distribution, differentiation and migration through transmembrane receptors coupled to heterotrimeric GTP‐binding proteins. Among various chemokines, stromal cell‐derived factor‐1 (SDF‐1α/CXCL12) seems to be a key chemokine to control endothelial cell migration. The aim of this study was to examine whether muscle contractile activity regulates CXCL12 expression in skeletal muscle.MethodsMale C57BL/6 mice were individually housed in cages equipped with a running wheel for 4 weeks. Oxidative soleus, plantaris and gastrocnemius with mixed fiber types, and glycolytic white vastus lateralis muscle were harvested at 24 hours after exercise training periods to measure mRNA expression and protein. Gastrocnemius muscle was harvested from muscle‐specific PGC‐1α transgenic mice (PGC‐1αTg) to measure CXCL12 protein. C2C12 myoblasts and myotubes were cultured for 1, 6 and 24 hours with or without mechanical stretch. Total RNA was isolated at 1 and 6 hours after stretch to measure CXCL12 mRNA expression. Protein was isolated at 24 hours after stretch to measure CXCL12 protein. Medium from cultured C2C12 myoblasts and myotubes were also collected at 24 hours after stretch to measure CXCL12 protein.ResultsCXCL12 mRNA and protein in soleus muscle was higher than white vastus lateralis muscle. Voluntary running resulted in increased CXCL12 mRNA and protein in gastrocnemius muscle. PGC‐1αTg mice expressed higher CXCL12 protein compared to wild‐type littermate. Mechanical stretch increased CXCL12 mRNA but not protein in C2C12 myotube. CXCL12 protein in medium from stretched C2C12 myotube increased by mechanical stretch. CXCL12 mRNA expression and protein in C2C12 myoblast has no effect to mechanical stretch.ConclusionsMuscle contractile activity regulates CXCL12 expression in skeletal muscle, which may contribute to exercise‐induced angiogenesis in skeletal muscle.Support or Funding InformationGrant‐in‐Aid for Challenging Exploratory Research (16K13019) and Grant‐in‐Aid for Scientific Research (B) (15H03080) to Okutsu M.

Estrogen modulates the contribution of neuropeptide Y to baseline hindlimb blood flow control in female Sprague-Dawley rats

The purpose of this study was to determine the role of estrogen in neuropeptide Y (NPY) and Y(1) receptor (Y(1)R)-mediated vascular responses in female rats. Based on earlier work from our laboratory that female rats lacked an NPY contribution to hindlimb vascular conductance relative to males, we tested the hypothesis that estrogen modulates Y(1)R-mediated hindlimb blood flow control. Thus it was expected that ovariectomy would: 1) increase skeletal muscle Y(1)R expression, 2) decrease skeletal muscle Y(2) receptor (Y(2)R) expression, 3) decrease peptidase activity, and/or 4) increase overall skeletal muscle NPY concentration. Separate groups of control (CTL), ovariectomized (OVX), and OVX + 17beta-estradiol replacement (OVX + E(2); 21-day pellet) rats were studied. Animals were anesthetized and given localized hindlimb delivery of BIBP-3226 (Y(1)R antagonist), while femoral artery blood flow and blood pressure were recorded. Tissue samples from the white and red vastus lateralis muscle were extracted to examine Y(1)R and Y(2)R expression, peptidase activity, and NPY concentration. We found that Y(1)R blockade resulted in increased baseline hindlimb blood flow and vascular conductance in OVX rats, whereas no change was noted in CTL or OVX + E(2) groups (P < 0.05). This enhanced functional effect in the OVX group aligned with greater skeletal muscle Y(1)R expression in white vastus muscle and a substantial increase in NPY concentration in both white and red vastus muscle compared with CTL and OVX + E(2) groups. There was no change in Y(2)R expression or peptidase activity among the groups. These data support the hypothesis that estrogen blunts Y(1)R activation in the rat hindlimb through an effect on Y(1)R expression and NPY concentration.

Fiber Type-Specific Nitric Oxide Protects Oxidative Myofibers against Cachectic Stimuli

Oxidative skeletal muscles are more resistant than glycolytic muscles to cachexia caused by chronic heart failure and other chronic diseases. The molecular mechanism for the protection associated with oxidative phenotype remains elusive. We hypothesized that differences in reactive oxygen species (ROS) and nitric oxide (NO) determine the fiber type susceptibility. Here, we show that intraperitoneal injection of endotoxin (lipopolysaccharide, LPS) in mice resulted in higher level of ROS and greater expression of muscle-specific E3 ubiqitin ligases, muscle atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger-1 (MuRF1), in glycolytic white vastus lateralis muscle than in oxidative soleus muscle. By contrast, NO production, inducible NO synthase (iNos) and antioxidant gene expression were greatly enhanced in oxidative, but not in glycolytic muscles, suggesting that NO mediates protection against muscle wasting. NO donors enhanced iNos and antioxidant gene expression and blocked cytokine/endotoxin-induced MAFbx/atrogin-1 expression in cultured myoblasts and in skeletal muscle in vivo. Our studies reveal a novel protective mechanism in oxidative myofibers mediated by enhanced iNos and antioxidant gene expression and suggest a significant value of enhanced NO signaling as a new therapeutic strategy for cachexia.

NO‐dependent up‐regulation of antioxidant genes protects oxidative myofibers from cachectic stimuli in mice

Oxidative skeletal muscles are more resistant than glycolytic muscles to cachexia caused by chronic heart failure and other chronic diseases. The molecular mechanism for the protection associated with oxidative phenotype remains elusive. We hypothesized that differential regulation of antioxidant gene expression accounts for the fiber type susceptibility. Here, we show that intraperitoneal injection of endotoxin (lipopolysaccharide, LPS) resulted in higher level of reactive oxygen species (ROS) and greater expression of muscle‐specific E3 ubiqitin ligases, muscle atrophy F‐box (MAFbx)/atrogin‐1 and muscle RING finger‐1 (MuRF1), in mouse glycolytic white vastus lateralis muscle than in oxidative soleus muscle. By contrast, nitric oxide (NO) production, inducible NO synthase (iNOS) and antioxidant gene expression were greatly enhanced in oxidative, but not in glycolytic muscles, suggesting that NO mediates protection against muscle wasting. NO donors enhanced iNos and antioxidant gene expression and blocked cytokine/endotoxin‐induced MAFbx/atrogin‐1 expression in cultured myoblasts and in skeletal muscle in vivo. Our studies reveal a novel protective mechanism in oxidative myofibers mediated by enhanced iNos and antioxidant gene expression and significant value of enhanced NO signaling as a new therapeutic strategy for cachexia.

Oxidative Phenotype Protects Myofibers from Pathological Insults Induced by Chronic Heart Failure in Mice

The fiber specificity of skeletal muscle abnormalities in chronic heart failure (CHF) has not been defined. We show here that transgenic mice (8 weeks old) with cardiac-specific overexpression of calsequestrin developed CHF (50.9% decrease in fractional shortening and 56.4% increase in lung weight, P<0.001), cachexia (37.8% decrease in body weight, P<0.001), and exercise intolerance (69.3% decrease in running distance to exhaustion, P<0.001) without a significant change in muscle fiber-type composition. Slow oxidative soleus muscle maintained muscle mass, whereas fast glycolytic tibialis anterior and plantaris muscles underwent atrophy (11.6 and 13.3%, respectively; P<0.05). In plantaris muscle, glycolytic type IId/x and IIb, but not oxidative type I and IIa, fibers displayed significant decreases in cross-sectional area (20.3%, P<0.05). Fast glycolytic white vastus lateralis muscle showed sarcomere degeneration and decreased cytochrome c oxidase IV (39.5%, P<0.01) and peroxisome proliferator-activated receptor gamma co-activator 1alpha protein expression (30.3%, P<0.01) along with a dramatic induction of the MAFbx/Atrogin-1 mRNA. These findings suggest that exercise intolerance can occur in CHF without fiber type switching in skeletal muscle and that oxidative phenotype renders myofibers resistant to pathological insults induced by CHF.

Skeletal muscle Ca(2+)-independent kinase activity increases during either hypertrophy or running.

Spikes in free Ca(2+) initiate contractions in skeletal muscle cells, but whether and how they might signal to transcription factors in skeletal muscles of living animals is unknown. Since previous studies in non-muscle cells have shown that serum response factor (SRF) protein, a transcription factor, is phosphorylated rapidly by Ca(2+)/calmodulin (CaM)-dependent protein kinase after rises in intracellular Ca(2+), we measured enzymatic activity that phosphorylates SRF (designated SRF kinase activity). Homogenates from 7-day-hypertrophied anterior latissimus dorsi muscles of roosters had more Ca(2+)-independent SRF kinase activity than their respective control muscles. However, no differences were noted in Ca(2+)/CaM-dependent SRF kinase activity between control and trained muscles. To determine whether the Ca(2+)-independent and Ca(2+)/CaM-dependent forms of Ca(2+)/CaM-dependent protein kinase II (CaMKII) might contribute to some of the SRF kinase activity, autocamtide-3, a synthetic substrate that is specific for CaMKII, was employed. While the Ca(2+)-independent form of CaMKII was increased, like the Ca(2+)-independent form of SRF kinase, no alteration in CaMKII occurred at 7 days of stretch overload. These observations suggest that some of SRF phosphorylation by skeletal muscle extracts could be due to CaMKII. To determine whether this adaptation was specific to the exercise type (i.e., hypertrophy), similar measurements were made in the white vastus lateralis muscle of rats that had completed 2 wk of voluntary running. Although Ca(2+)-independent SRF kinase was increased, no alteration occurred in Ca(2+)/CaM-dependent SRF kinase activity. Thus any role of Ca(2+)-independent SRF kinase signaling has downstream modulators specific to the exercise phenotype.

Cocaine and exercise: alpha-1 receptor blockade does not alter muscle glycogenolysis or blood lactacidosis.

In our previous work, we routinely observed that a combined cocaine-exercise challenge results in an abnormally rapid muscle glycogen depletion and excessive blood lactacidosis. These phenomena occur simultaneously with a rapid rise in norepinephrine and in the absence of any rise in epinephrine. We postulated that norepinephrine may cause vasoconstriction of the muscle vasculature through activation of alpha-1 receptors during cocaine-exercise, thus inducing hypoxia and a concomitant rise in glycogenolysis and lactate accumulation. To test this hypothesis, rats were pretreated with the selective alpha-1-receptor antagonist prazosin (P) (0.1 mg/kg iv) or saline (S). Ten minutes later, the animals were treated with cocaine (-C) (5 mg/kg iv) or saline (-S) and run for 4 or 15 min at 22 m/min at 10% grade. In the S-S group, glycogen content of the white vastus lateralis muscle was unaffected by exercise at both time intervals, whereas in S-C rats glycogen was reduced by 47%. This effect of cocaine-exercise challenge was not attenuated by P. Similarly, blood lactate concentration in S-C rats was threefold higher than that of S-S after exercise, a response also not altered by pretreatment with P. On the basis of these observations, we conclude that the excessive glycogenolysis and lactacidosis observed during cocaine-exercise challenge is not the result of vasoconstriction secondary to norepinephrine activation of alpha-1 receptors.

Cytochrome c promoter activity in soleus and white vastus lateralis muscles in rats.

Cytochrome c protein and mRNA are 300 and 100% higher, respectively, in the soleus muscle (predominantly slow-twitch oxidative) than the white vastus lateralis (predominately fast-twitch glycolytic) muscle (W. W. Winder, K. M. Baldwin, and J. O. Holloszy. Eur. J. Biochem. 47: 461-467, 1974; M. M. Lai and F. W. Booth. J. Appl. Physiol. 69: 843-848, 1990). However, the mechanisms controlling these differences in cytochrome c mRNA are largely unknown. The present study employed direct plasmid injection techniques to determine whether the proximal promoter (-726 to +610) of the rat somatic cytochrome c gene was more active in the soleus than in white vastus lateralis muscles in rats. No difference between the soleus and white vastus lateralis muscles for the activities of the -726, -631, -489, -326, -215, -159 and -149 cytochrome c promoters was noted. The results of this study suggest that additional elements (outside of -726 to +610) in the cytochrome c gene may be required, or posttranscriptional regulation may account, for the higher cytochrome c mRNA in the slow-twitch oxidative muscle.

EXERCISE GLYCOGEN DEPLETION PATTERNS IN TRAINED RATS ADAPTED TO A HIGH-FAT OR HIGH-CARBOHYDRATE DIET 5

Research has shown that trained rats adapted to a high-fat diet (HF) can run longer than rats consuming a high-carbohydrate diet (HC). One proposed mechanism to explain this phenomena is an adaptation in muscle that spares glycogen during exercise. This study compared glycogen depletion patterns in endurance-trained rats adapted to a HF or HC. Male Sprague-Dawley rats (n=48, 200+g) were progressively treadmill trained over 8 wks to where they were running 60 min/d, 5d/wk. Half the group was consuming a HF (fat = 78% of kcal) while half consumed a HC (69% carbohydrate). On the day of the experiment, 6 rats per diet were run at 29 m/min, 8% grade for 0, 10, 20, or 60 min. Immediately post-exercise rats were anesthetized, and soleus (S), red vastus lateralis (RV), and white vastus lateralis (WV) muscles removed. There were no significant differences between diets for S glycogen pre-, during, or post-exercise. RV glycogen (μM/g wet wt) was lower (*p<0.05)at rest in the HF group, 27.5±3.9,* HF vs. 37.6±3.5, HC(Mean±SEM, ANOVA), but similar to HC at 60 min (11.0±1.9, HF vs. 8.6±1.3, HC). At 10 min, RV glycogen remaining was 64.2±10.7%,* HF vs. 57.5±3.9%, HC; at 20 min, 51.2±10.1%,* HF vs. 29.7±5.4%, HC; at 60 min 50.2±10.6%,* HF vs. 29.6±5.1%, HC. RV glycogen use rates(μM/g/10 min) were lower in HF (9.85±2.95,* 3.56±0.61*) than in HC rats (15.93±1.44, 14.06±3.62) for 0-10 and 10-20 min, respectively. Resting WV glycogen was 25.33±1.63,* HF; 40.65±5.80, HC while post-exercise values were 17.02±4.39, HF and 15.70±2.70. Glycogen use rates between 10-20 min were also lower in the HF (0.23±0.49*) compared to the HC (16.01±1.77). These data indicate that muscle glycogen is spared during prolonged exercise in HF adapted rats and that the sparing occurs according to expected muscle recruitment patterns during prolonged exercise.

Effect of estradiol on the temporal pattern of exercise-induced tissue glycogen depletion in male rats

The effect of 17 beta-estradiol 3-benzoate (10 micrograms.01 ml of sunflower oil-1 x 100 g body wt-1) on the temporal pattern of exercise-induced tissue glycogen depletion and tissue lipid availability during submaximal treadmill running was determined in male rats. Animal were administered estradiol or oil for 5 days and were then time matched for motorized treadmill running for 30, 60, 90, or 120 min. Significant depletion of liver, soleus muscle, and red and white vastus lateralis muscle tissue glycogen occurred in oil-administered animals run between 30 and 120 min. The greatest extent of tissue glycogen depletion occurred during the first 30 min of exercise with the rate of glycogen depletion slowing between 30 and 120 min of exercise. Administration of estradiol attenuated the temporal pattern of glycogen depletion in both liver and muscle tissues. Significant depletion of red and white vastus glycogen of estradiol-administered animals did not occur until 90 and 120 min of exercise, respectively. Administration of estradiol significantly increased resting plasma free fatty acids and red and white vastus triacylglycerol content. These data indicate that estradiol administration for 5 days resulted in significant glycogen sparing of liver and muscle tissues during submaximal treadmill running for up to 120 min by altering the temporal pattern of glycogen depletion of male rats secondary to an estradiol-mediated increase in availability of lipid substrate during exercise.

Energy balance and lipid metabolism in transgenic mice bearing an antisense GCR gene construct.

Energy balance and lipid metabolism were investigated in transgenic mice bearing an antisense glucocorticoid receptor (GCR) gene construct that impairs the normal expression of the GCR gene. Food intake was recorded during the 15 days preceding decapitation of adult normal and transgenic mice, and feces were collected to derive the digestible energy intake. Body composition measurements consisted of the determination of energy, protein, and fat content of the carcass. Carcass energy was determined by bomb calorimetry, whereas carcass protein was measured by the Kjeldahl procedure. Energy expenditure was estimated from the continuous oxygen consumption (VO2) monitoring over a 24-h period. Lipoprotein lipase (LPL) activity was quantified in epididymal white adipose tissue (WAT), heart, and vastus lateralis muscle (VLM) by measuring the in vitro hydrolysis of labeled triolein in the presence of tissue homogenates. Norepinephrine (NE) content of both interscapular brown adipose tissue (BAT) and heart were determined by high-performance liquid chromatography (HPLC). Energy intake and expenditure were significantly lower in transgenic mice than in controls. Concurrently, both fat content and total energy of the carcasses were significantly higher in the transgenic animals. In comparison with normal mice, heart and VLM LPL activity was significantly reduced in transgenic mutants. There was no difference between groups in LPL activity in WAT. Finally, heart and BAT NE contents were lower in transgenic animals than in control mice. These results suggest that a defective GCR system may affect energy balance through increasing energetic efficiency, and they emphasize the modulatory effects of hypothalamic-pituitary-adrenal axis changes on muscle LPL activity.

Effect of training and detraining on skeletal muscle glucose transporter (GLUT4) content in rats.

The aim of the present study was to examine the effects of treadmill exercise training and detraining on the skeletal muscle fiber type specific expression of the insulin-regulated glucose transporter protein (GLUT4) in rats. GLUT4 protein content was determined by Western and dot-blot analysis, using a polyclonal antibody raised against the carboxy-terminal peptide. Rats were sacrificed 24 h after the last training session. There were no significant changes in muscle GLUT4 after 1 day or 1 week of training. Six weeks of training increased GLUT4 protein content 1.4- to 1.7-fold (p < 0.05) over controls in the soleus and red vastus lateralis, whereas no significant change was evident in the white vastus lateralis muscle. GLUT4 protein content in both soleus and red vastus lateralis muscle returned to near control values after 7 days of detraining. Similar to GLUT4, citrate synthase activity showed no change after 1 day or 1 week of training, increased 1.8-fold over controls after 6 weeks of training, but returned to control values after 7 days detraining. These findings demonstrate that muscle GLUT4 protein is increased in rats with as little as 6 weeks of treadmill exercise training but that the adaptation is lost within 1 week of detraining. It is suggested that expression of the GLUT4 protein is coordinated with the well-documented adaptations in oxidative enzyme activity with endurance training and detraining.

Regulation of lipoprotein lipase in adipose and muscle tissues during fasting

The purpose of this work was to determine the relationship between lipoprotein lipase (LPL) activity and LPL mRNA in muscle and adipose tissue in fed and fasted rats. In control animals, the correlation between enzyme activity and LPL mRNA for adipose tissue, heart, soleus, fast red vastus lateralis, and fast white vastus lateralis muscle was r = +0.97. Twenty-four hours of fasting increased LPL activity 38% in heart, reduced it 59% in adipose tissue, and had no effect on activity in the three skeletal muscles analyzed. At the same time, relative LPL mRNA concentrations were reduced 25% in adipose tissue and elevated in heart, soleus, red vastus, and white vastus muscles when compared with control concentrations. Prolonging the fast to 6 days was accompanied by a 64% reduction in adipose tissue LPL activity and an increase in the activities of slow-twitch soleus (83%) and fast-twitch red vastus lateralis muscles (193%), with no enzyme activity change in heart or white vastus lateralis muscle compared with values obtained from control fed animals. LPL mRNA concentration was reduced 66% in adipose tissue, increased more than twofold in heart, soleus, and white vastus muscle, and increased threefold in red vastus muscle. Changes in relative LPL mRNA concentration in adipose tissue induced by fasting could, in part, be accounted for by the increases seen in total RNA concentration. The relationships between enzyme activity and LPL mRNA in muscle and adipose tissue were r = 0.97 and 0.77 for 1-day and 6-day fasted animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cocaine on plasma catecholamine and muscle glycogen concentrations during exercise in the rat

This study was designed to test the hypothesis that cocaine (C) alters the normal physiological responses to exercise. Male rats were injected with saline (S) or C (12.5 mg/kg) either intravenously (iv) or intraperitoneally (ip). After injection the animals were allowed to rest for 30 min or were run on the treadmill (26 m/min, 10% grade). At rest plasma epinephrine values were 245 +/- 24 pg/ml in the S group and 411 +/- 43 (ip) and 612 +/- 41 (iv) pg/ml in the C groups (P less than 0.05 between S and C). During exercise plasma epinephrine levels were 615 +/- 32 pg/ml in S and 1,316 +/- 58 (ip) and 1,208 +/- 37 (iv) pg/ml in the C groups (P less than 0.05 between S and C). Similar results were obtained for norepinephrine. Glycogen content in the white vastus lateralis muscle was reduced to 31 +/- 2 mumol/g in S after exercise, but after C and exercise the values were 12 +/- 4 (ip) and 16 +/- 3 (iv) mumol/g (P less than 0.05 between S and C). There was no effect of the drug on this parameter at rest. Blood lactate rose to 4.8 +/- 1.0 (ip) and 5.8 +/- 1.3 (iv) mM in the C groups but to only 3.0 +/- 0.2 in the S group after exercise (P less than 0.05 between S and C). These results show that C and exercise combined exert a more dramatic effect on plasma catecholamine, muscle glycogen, and blood lactate concentrations than do C and exercise alone. They provide further insight into explaining the adverse effects of C on exercise endurance observed previously (Bracken et al., J. Appl. Physiol. 66: 377-383, 1989).

Effects of Increased Training Volume on the Oxidative Capacity, Glycogen Content and Tension Development of Rat Skeletal Muscle

This study examined the effects of a short-term sudden increment in training load on the oxidative capacity, glycogen content and tension-generating ability of rat skeletal muscle. After training on a treadmill 5 dwk-1 for 9 wk (30 m.min-1 6 degrees, 60 min.d-1), rats were randomly divided into a normal training volume (NTV) group (N = 11) and an increased training volume (ITV) group (N = 8). The NTV group were sacrificed 24 h after the last bout of exercise, while the ITV group continued to train for further 6 successive days. Training duration for this latter group was increased to 120 min.d-1 for the first 2 d; 240 min.d-1 for the next 2 d; and 360 min.d-1 for the final 2 d; speed and grade were kept constant. Respiratory capacity (QO2) and citrate synthase activity were increased (P less than 0.05) in both the soleus and plantaris muscles, with no change in the white vastus lateralis muscle of the NTV group when compared to age- matched sedentary controls. Glycogen levels were unchanged in these muscles, but liver glycogen content was greater (231.9 +/- 10.1 vs 156.8 +/- 15.3 umol.g-1 w.w. for the NTV vs age-matched sedentary controls, respectively, P less than 0.05). Peak tetanic tension in the gastrocnemius was not changed by training, or the increased training load. Citrate synthase activity (umol.min-1.g-1) was significantly greater (P less than 0.05) in the plantaris (33.3 +/- 1.0 vs 27.0 +/- 1.7) and soleus muscles (40.5 +/- 2.7 vs 28.4 +/- 1.3) in the ITV vs NTV groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of endurance exercise on isomyosin patterns in fast- and slow-twitch skeletal muscles

Although endurance training has been shown to profoundly affect the oxidative capacity of skeletal muscle, little information is available concerning the impact of endurance training on skeletal muscle isomyosin expression across a variety of muscle fiber types. Therefore, a 10-wk running program (1 h/day, 5 days/wk, 20% grade, 1 mile/h) was conducted to ascertain the effects of endurance training on isomyosin expression in the soleus, vastus intermedius (VI), plantaris (PLAN), red and white medial gastrocnemius (RMG and WMG), and red and white vastus lateralis muscles (RVL and WVL). Evidences of training were noted by the presence of a resting and a submaximal exercise bradycardia, as well as an enhancement in peak O2 consumption in the trained rodents relative to the nontrained controls. No evidence for skeletal muscle hypertrophy was observed subsequent to training when muscle weight was normalized to body weight. Shifts in the isomyosin profile of the trained VI, RMG, RVL, and PLAN were seen relative to the nontrained controls. Specifically, training affected the slow myosin (SM) composition of the VI by decreasing the relative content of the SM2 isoform by 14% while increasing that of the SM1 isoform (P less than 0.05). In addition, training elicited various degrees of a fast to slower myosin transformation in the RMG, RVL, and PLAN. All three muscles showed a significant reduction in the fast myosin 2 isoform (P less than 0.05), with significant increases in intermediate myosin in the RVL and PLAN along with elevations in SM2 in the RMG and PLAN (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Epinephrine activation of heparin-nonreleasable lipoprotein lipase in 3 skeletal muscle fiber types of the rat

Epinephrine was used to activate the heparin non-releasable lipoprotein lipase (LPL) in the 3 skeletal muscle fiber types of the perfused rat hindlimb. Following a 9 min washout of the capillary-bound lipoprotein lipase, the hindquarter of the rat was perfused with a buffer containing 10 nM of epinephrine. Activity of the residual LPL in soleus, red vastus lateralis, and white vastus lateralis muscles increased 75%, 96%, and 102% respectively, following epinephrine perfusion. These results suggest that skeletal muscle LPL is under hormonal control possibly through protein phosphorylation by cyclic AMP dependent protein kinase.