GPR30 ACTIVATION IMPROVES EXERCISE CAPACITY AND SKELETAL MUSCLE FUNCTION IN SENESCENT FEMALE F344BN RATS

e13002 Background: The neuropsychological impact of malignant glioma is well documented; the physiological and functional effects are not known. We conducted a pilot study to quantitatively assess cardiorespiratiory fitness, skeletal muscle function, and body composition of patients with primary malignant glioma. Methods: Using a cross-sectional design, patients with clinically stable postsurgical (10 ± 7 days post surgery) high-grade glioma (HGG; n=25) and low-grade glioma (LGG) were studied. Participants performed a cardiopulmonary exercise test (CPET) with expired gas analysis to assess peak exercise capacity (VO2peak) and other parameters of cardiovascular function. Other physiological outcomes included skeletal muscle cross-sectional area (CSA; magnetic resonance imaging), isokinetic muscle strength (isokinetic dynamometer), and body composition (air displacement plethysmography). QOL was assessed by the Functional Assessment of Cancer Therapy-Brain scale (FACT-BR). Results: CPET was a feasible and safe procedure for malignant glioma patients with no serious adverse events. Peak VO2 indexed to total body weight and lean body mass for both groups was 13.0 mL.min-1 and 19 mL.min-1; the equivalent to 59% and 38% below age and sex-predicted normative values, respectively. Skeletal muscle isokinetic strength was significantly lower in HGG relative to LGG patients (83 vs. 125 Nm, p=.025) and predicted peak VO2 (r = 0.44, p<0.05). In patients with HGG, only self-reported exercise behavior was correlated with QOL (r = 0.42; p=.046) while sex (male) (r = 0.44; p=.037), lean mass (r = -0.41; p=.049), and VO2peak (r = -0.40; p=.052) were associated with fatigue. Conclusions: CPET is a safe and feasible tool to evaluate physical functioning in select patients with malignant glioma. Postsurgical glioma patients have markedly reduced exercise capacity, isokinetic strength and CSA. Muscle strength is an important contributor to poor VO2peak in this population. Prospective studies are now required to determine whether such abnormalities influence prognosis as well as test the effect of appropriately selected interventions to prevent and/or mitigate dysfunction. No significant financial relationships to disclose.

Download Full-text

Maximal exercise capacity and peripheral skeletal muscle function following lung transplantation

The Journal of Heart and Lung Transplantation ◽

10.1016/s1053-2498(98)00027-8 ◽

1999 ◽

Vol 18 (2) ◽

pp. 113-120 ◽

Cited By ~ 69

Author(s):

Larry C Lands ◽

Argyrios A Smountas ◽

Giulia Mesiano ◽

L Brosseau ◽

Hani Shennib ◽

...

Keyword(s):

Skeletal Muscle ◽

Lung Transplantation ◽

Exercise Capacity ◽

Muscle Function ◽

Maximal Exercise ◽

Skeletal Muscle Function ◽

Maximal Exercise Capacity

Download Full-text

Impaired exercise capacity and skeletal muscle function in a mouse model of pulmonary inflammation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00607.2012 ◽

2013 ◽

Vol 114 (9) ◽

pp. 1340-1350 ◽

Cited By ~ 12

Author(s):

Kechun Tang ◽

George Murano ◽

Harrieth Wagner ◽

Leonardo Nogueira ◽

Peter D. Wagner ◽

...

Keyword(s):

Skeletal Muscle ◽

Exercise Capacity ◽

Muscle Function ◽

Citrate Synthase ◽

Left Ventricular ◽

Lv Function ◽

Male Mice ◽

Skeletal Muscle Function ◽

Exercise Limitation ◽

Maximal Pressure

Pulmonary TNFα has been linked to reduced exercise capacity in a subset of patients with moderate to severe chronic obstructive pulmonary disease (COPD). We hypothesized that prolonged, high expression of pulmonary TNFα impairs cardiac and skeletal muscle function, and both contribute to exercise limitation. Using a surfactant protein C promoter-TNFα construct, TNFα was overexpressed throughout life in mouse lungs (SP-C/TNFα+). TNFα levels in wild-type (WT) female serum and lung were two- and threefold higher than in WT male mice. In SP-C/TNFα+ mice, TNFα increased similarly in both sexes. Treadmill exercise was impaired only in male SP-C/TNFα+ mice. While increases in lung volume and airspace size induced by TNFα were comparable in both sexes, pulmonary hypertension along with lower body and muscle mass were evident only in male mice. Left ventricular (LV) function (cardiac output, stroke volume, LV maximal pressure, and LV maximal pressure dP/d t) was not altered by TNFα overexpression. Fatigue measured in isolated soleus and EDL was more rapid only in soleus of male SP-C/TNFα+ mice and accompanied by a loss of oxidative IIa fibers, citrate synthase activity, and PGC-1α mRNA and increase in atrogin-1 and MuRF1 expression also only in male mice. In situ gastrocnemius fatigue resistance, reflecting both oxygen availability and contractility, was decreased similarly in female and male SP-C/TNFα+ mice. These data indicate that male, but not female, mice overexpressing pulmonary TNFα are susceptible to exercise limitation, possibly due to muscle wasting and loss of the oxidative muscle phenotype, with protection in females possibly due to estrogen.

Download Full-text

Relationship between intermuscular adipose tissue infiltration and myostatin before and after aerobic exercise training

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00030.2018 ◽

2018 ◽

Vol 315 (3) ◽

pp. R461-R468 ◽

Cited By ~ 11

Author(s):

Adam R. Konopka ◽

Christopher A. Wolff ◽

Miranda K. Suer ◽

Matthew P. Harber

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Exercise Training ◽

Aerobic Exercise ◽

Exercise Capacity ◽

Muscle Function ◽

Aerobic Exercise Training ◽

Skeletal Muscle Function ◽

Intermuscular Adipose Tissue ◽

Before And After

Intermuscular adipose tissue (IMAT) is associated with impaired skeletal muscle contractile and metabolic function. Myostatin and downstream signaling proteins such as cyclin-dependent kinase 2 (CDK2) contribute to the regulation of adipose and skeletal muscle mass in cell culture and animals models, but this relationship remains incompletely understood in humans. The purpose of this study was to determine if the infiltration of IMAT was associated with skeletal muscle myostatin and downstream proteins before and after 12 wk of aerobic exercise training (AET) in healthy older women (OW; 69 ± 2 yr), older men (OM; 74 ± 3 yr), and young men (YM; 20 ± 1 yr). We found that the infiltration of IMAT was correlated with myostatin and phosphorylated CDK2 at tyrosine 15 [P-CDK2(Tyr15)]. IMAT infiltration was greater in the older subjects and was associated with lower skeletal muscle function and exercise capacity. After 12 wk of AET, there was no change in body weight. Myostatin and P-CDK2(Tyr15) were both decreased after AET, and the reduction in myostatin was associated with decreased IMAT infiltration. The decrease in myostatin and IMAT occurred concomitantly with increased exercise capacity, skeletal muscle size, and function after AET. These findings demonstrate that the reduction in IMAT infiltration after AET in weight stable individuals was accompanied by improvements in skeletal muscle function and exercise capacity. Moreover, the association between myostatin and IMAT was present in the untrained state and in response to exercise training, strengthening the potential regulatory role of myostatin on IMAT.

Download Full-text

Combination of Exercise Training and Diet Restriction Normalizes Limited Exercise Capacity and Impaired Skeletal Muscle Function in Diet-Induced Diabetic Mice

Endocrinology ◽

10.1210/en.2013-1382 ◽

2014 ◽

Vol 155 (1) ◽

pp. 68-80 ◽

Cited By ~ 18

Author(s):

Tadashi Suga ◽

Shintaro Kinugawa ◽

Shingo Takada ◽

Tomoyasu Kadoguchi ◽

Arata Fukushima ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Exercise Training ◽

Exercise Capacity ◽

Muscle Function ◽

Normal Diet ◽

Diabetic Mice ◽

Diet Restriction ◽

Skeletal Muscle Function

Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

Download Full-text

Faculty Opinions recommendation of TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1556023.1047131 ◽

2010 ◽

Author(s):

Annemie Schols ◽

Harry Gosker

Keyword(s):

Skeletal Muscle ◽

Cigarette Smoke ◽

Muscle Function ◽

Smoke Exposure ◽

Tnf Alpha ◽

Cigarette Smoke Exposure ◽

Skeletal Muscle Function ◽

Mediated Reduction

Download Full-text

Skeletal muscle dysfunction in chronic renal failure: effects of exercise

AJP Renal Physiology ◽

10.1152/ajprenal.00296.2005 ◽

2006 ◽

Vol 290 (4) ◽

pp. F753-F761 ◽

Cited By ~ 77

Author(s):

Gregory R. Adams ◽

Nosratola D. Vaziri

Keyword(s):

Skeletal Muscle ◽

Renal Failure ◽

Exercise Capacity ◽

Muscle Function ◽

Chronic Illnesses ◽

Treatment Modalities ◽

Muscle Dysfunction ◽

Obstructive Pulmonary Disease ◽

Skeletal Muscle Dysfunction

A number of chronic illnesses such as renal failure (CRF), obstructive pulmonary disease, and congestive heart failure result in a significant decrease in exercise tolerance. There is an increasing awareness that prescribed exercise, designed to restore some level of physical performance and quality of life, can be beneficial in these conditions. In CRF patients, muscle function can be affected by a number of direct and indirect mechanisms caused by renal disease as well as various treatment modalities. The aims of this review are twofold: first, to briefly discuss the mechanisms by which CRF negatively impacts skeletal muscle and, therefore, exercise capacity, and, second, to discuss the available data on the effects of programmed exercise on muscle function, exercise capacity, and various other parameters in CRF.

Download Full-text