MyoView: Fully-automated image segmentation method to analyse skeletal muscle cross section in exercise-induced regenerating myofibers

AbstractSkeletal muscle is an adaptive tissue with the ability to regenerate in response to exercise training. Cross-sectional area (CSA) quantification, as a main parameter to assess muscle regeneration capability, is highly tedious and time-consuming, necessitating an accurate and automated approach to analysis. Although several excellent programs are available to automate analysis of muscle histology, they fail to efficiently and accurately measure CSA in regenerating myofibers in response to exercise training. Here, we have developed a novel fully-automated image segmentation method based on neutrosophic set algorithms to analyse whole skeletal muscle cross sections in exercise-induced regenerating myofibers, referred as MyoView, designed to obtain accurate fiber size and distribution measurements. MyoView provides relatively efficient, accurate, and reliable measurements for detecting different myofibers and CSA quantification in response to the post-exercise regenerating process. We showed that MyoView is comparable with manual quantification. We also showed that MyoView is more accurate and efficient to measure CSA in post-exercise regenerating myofibers as compared with Open-CSAM, MuscleJ, SMASH and MyoVision. Furthermore, we demonstrated that to obtain an accurate CSA quantification of exercise-induced regenerating myofibers, whole muscle cross-section analysis is an essential part, especially for the measurement of different fiber-types. We present MyoView as a new tool for CSA quantification in skeletal muscle from any experimental condition including exercise-induced regenerating myofibers.

Automated image segmentation method to analyse skeletal muscle cross section in exercise-induced regenerating myofibers

Scientific Reports ◽

10.1038/s41598-021-00886-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Masoud Rahmati ◽

Abdolreza Rashno

Keyword(s):

Skeletal Muscle ◽

Image Segmentation ◽

Exercise Training ◽

Cross Section ◽

Satellite Cells ◽

Neutrosophic Set ◽

Segmentation Method ◽

Post Exercise ◽

Exercise Induced ◽

AbstractSkeletal muscle is an adaptive tissue with the ability to regenerate in response to exercise training. Cross-sectional area (CSA) quantification, as a main parameter to assess muscle regeneration capability, is highly tedious and time-consuming, necessitating an accurate and automated approach to analysis. Although several excellent programs are available to automate analysis of muscle histology, they fail to efficiently and accurately measure CSA in regenerating myofibers in response to exercise training. Here, we have developed a novel fully-automated image segmentation method based on neutrosophic set algorithms to analyse whole skeletal muscle cross sections in exercise-induced regenerating myofibers, referred as MyoView, designed to obtain accurate fiber size and distribution measurements. MyoView provides relatively efficient, accurate, and reliable measurements for CSA quantification and detecting different myofibers, myonuclei and satellite cells in response to the post-exercise regenerating process. We showed that MyoView is comparable with manual quantification. We also showed that MyoView is more accurate and efficient to measure CSA in post-exercise regenerating myofibers as compared with Open-CSAM, MuscleJ, SMASH and MyoVision. Furthermore, we demonstrated that to obtain an accurate CSA quantification of exercise-induced regenerating myofibers, whole muscle cross-section analysis is an essential part, especially for the measurement of different fiber-types. We present MyoView as a new tool to quantify CSA, myonuclei and satellite cells in skeletal muscle from any experimental condition including exercise-induced regenerating myofibers.

Exercise-induced mitogen-activated protein kinase signalling in skeletal muscle

Proceedings of The Nutrition Society ◽

10.1079/pns2004346 ◽

2004 ◽

Vol 63 (2) ◽

pp. 227-232 ◽

Cited By ~ 48

Author(s):

Yun Chau Long ◽

Ulrika Widegren ◽

Juleen R. Zierath

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Muscle Contraction ◽

Mitogen Activated Protein Kinase ◽

Mapk Cascades ◽

Extracellular Signal ◽

Mapk Signalling ◽

Mitogen Activated Protein ◽

Exercise Induced ◽

Exercise training improves glucose homeostasis through enhanced insulin sensitivity in skeletal muscle. Muscle contraction through physical exercise is a physiological stimulus that elicits multiple biochemical and biophysical responses and therefore requires an appropriate control network. Mitogen-activated protein kinase (MAPK) signalling pathways constitute a network of phosphorylation cascades that link cellular stress to changes in transcriptional activity. MAPK cascades are divided into four major subfamilies, including extracellular signal-regulated kinases 1 and 2, p38 MAPK, c-Jun NH2-terminal kinase and extracellular signal-regulated kinase 5. The present review will present the current understanding of parallel MAPK signalling in human skeletal muscle in response to exercise and muscle contraction, with an emphasis on identifying potential signalling mechanisms responsible for changes in gene expression.

Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00206.2004 ◽

2004 ◽

Vol 287 (6) ◽

pp. E1189-E1194 ◽

Cited By ~ 84

Author(s):

Christian P. Fischer ◽

Peter Plomgaard ◽

Anne K. Hansen ◽

Henriette Pilegaard ◽

Bengt Saltin ◽

...

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Muscle Glycogen ◽

Human Skeletal Muscle ◽

Acute Exercise ◽

Glycogen Content ◽

Knee Extensor ◽

Exercise Induced ◽

Response To Exercise ◽

Resting Muscle

Contracting skeletal muscle expresses large amounts of IL-6. Because 1) IL-6 mRNA expression in contracting skeletal muscle is enhanced by low muscle glycogen content, and 2) IL-6 increases lipolysis and oxidation of fatty acids, we hypothesized that regular exercise training, associated with increased levels of resting muscle glycogen and enhanced capacity to oxidize fatty acids, would lead to a less-pronounced increase of skeletal muscle IL-6 mRNA in response to acute exercise. Thus, before and after 10 wk of knee extensor endurance training, skeletal muscle IL-6 mRNA expression was determined in young healthy men ( n = 7) in response to 3 h of dynamic knee extensor exercise, using the same relative workload. Maximal power output, time to exhaustion during submaximal exercise, resting muscle glycogen content, and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase enzyme activity were all significantly enhanced by training. IL-6 mRNA expression in resting skeletal muscle did not change in response to training. However, although absolute workload during acute exercise was 44% higher ( P < 0.05) after the training period, skeletal muscle IL-6 mRNA content increased 76-fold ( P < 0.05) in response to exercise before the training period, but only 8-fold ( P < 0.05, relative to rest and pretraining) in response to exercise after training. Furthermore, the exercise-induced increase of plasma IL-6 ( P < 0.05, pre- and posttraining) was not higher after training despite higher absolute work intensity. In conclusion, the magnitude of the exercise-induced IL-6 mRNA expression in contracting human skeletal muscle was markedly reduced by 10 wk of training.

Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials.

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2021-0194 ◽

2021 ◽

Author(s):

Nanna Skytt Pilmark ◽

Laura Oberholzer ◽

Jens Frey Halling ◽

Jonas M. Kristensen ◽

Christina Pedersen Bønding ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Exercise Training ◽

Human Skeletal Muscle ◽

Acute Exercise ◽

Metformin Treatment ◽

Ampk Activation ◽

Double Blind ◽

Parallel Group ◽

Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant individuals and a double-blind, cross-over trial conducted in 15 healthy lean males) were included in this paper. In both studies, the effect of acute exercise +/- metformin treatment on different skeletal muscle variables, previously suggested to be involved in a pharmaco-physiological interaction between metformin and exercise, was assessed. Furthermore, in the parallel-group trial, the effect of 12 weeks of exercise training was assessed. Skeletal muscle biopsies were obtained before and after acute exercise and 12 weeks of exercise training, and mitochondrial respiration, oxidative stress and AMPK activation was determined. Metformin did not significantly affect the effects of acute exercise or exercise training on mitochondrial respiration, oxidative stress or AMPK activation, indicating that the response to acute exercise and exercise training adaptations in skeletal muscle is not affected by metformin treatment. Further studies are needed to investigate whether an interaction between metformin and exercise is present in other tissues, e.g. the gut. Trial registration: ClinicalTrials.gov (NCT03316690 and NCT02951260). Novelty bullets • Metformin does not affect exercise-induced alterations in mitochondrial respiratory capacity in human skeletal muscle • Metformin does not affect exercise-induced alterations in systemic levels of oxidative stress nor emission of reactive oxygen species from human skeletal muscle • Metformin does not affect exercise-induced AMPK activation in human skeletal muscle

Influence of training on skeletal muscle enzymatic adaptations in normal and diabetic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.249.4.e360 ◽

1985 ◽

Vol 249 (4) ◽

pp. E360-E365 ◽

Cited By ~ 2

Author(s):

E. G. Noble ◽

C. D. Ianuzzo

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Citrate Synthase ◽

Diabetic Rats ◽

Muscle Fiber Types ◽

Fiber Types ◽

Marker Enzymes ◽

Oxidative Potential ◽

Hydroxyacyl Coa Dehydrogenase ◽

Fast Twitch

Muscle homogenates representing slow-twitch oxidative, fast-twitch oxidative-glycolytic, fast-twitch glycolytic, and mixed fiber types were prepared from normal, diabetic, and insulin-treated diabetic rats. Diabetes was induced by injection of 80 mg . kg-1 of streptozotocin. The activities of citrate synthase, succinate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase were employed as markers of oxidative potential, whereas phosphorylase, hexokinase, and phosphofructokinase activities were used as an indication of glycolytic capacity. Diabetes was associated with a general decrement in the activity of oxidative marker enzymes for all fiber types except the fast-twitch glycolytic fiber. In contrast, the fast-twitch glycolytic fibers demonstrated the greatest decline in glycolytic enzymatic activity. Insulin-treated animals, either trained or untrained, exhibited enzyme activities similar to their normal counterparts. Exercise training of diabetic rats mimicked the effect of insulin treatment and caused a near normalization of the activity of the marker enzymes. These findings suggest that the enzymatic potential of all skeletal muscle fiber types of diabetic rats may be normalized by exercise training even in the absence of significant amounts of insulin.

The B2 Receptor of Bradykinin Is Not Essential for the Post-Exercise Increase in Glucose Uptake by Insulin-Stimulated Mouse Skeletal Muscle

Physiological Research ◽

10.33549/physiolres.932085 ◽

2011 ◽

pp. 511-519 ◽

Cited By ~ 7

Author(s):

G. G. SCHWEITZER ◽

C. M. CASTORENA ◽

T. HAMADA ◽

K. FUNAI ◽

E. B. ARIAS ◽

...

Keyword(s):

Skeletal Muscle ◽

Blood Glucose ◽

Glucose Uptake ◽

Insulin Action ◽

Plasma Insulin ◽

Treadmill Exercise ◽

Post Exercise ◽

Skeletal Muscle Glucose Uptake ◽

Glucose Plasma ◽

Bradykinin can enhance skeletal muscle glucose uptake (GU), and exercise increases both bradykinin production and muscle insulin sensitivity, but bradykinin’s relationship with post-exercise insulin action is uncertain. Our primary aim was to determine if the B2 receptor of bradykinin (B2R) is essential for the post-exercise increase in GU by insulin-stimulated mouse soleus muscles. Wildtype (WT) and B2R knockout (B2RKO) mice were sedentary or performed 60 minutes of treadmill exercise. Isolated soleus muscles were incubated with [3H]-2-deoxyglucose ±insulin (60 or 100 μU/ml). GU tended to be greater for WT vs. B2RKO soleus with 60 μU/ml insulin (P=0.166) and was significantly greater for muscles with 100 μU/ml insulin (P<0.05). Both genotypes had significant exercise-induced reductions (P<0.05) in glycemia and insulinemia, and the decrements for glucose (~14 %) and insulin (~55 %) were similar between genotypes. GU tended to be greater for exercised vs. sedentary soleus with 60 μU/ml insulin (P=0.063) and was significantly greater for muscles with 100 μU/ml insulin (P<0.05). There were no significant interactions between genotype and exercise for blood glucose, plasma insulin or GU. These results indicate that the B2R is not essential for the exercise-induced decrements in blood glucose or plasma insulin or for the post-exercise increase in GU by insulin-stimulated mouse soleus muscle.

Exercise: Teaching myocytes new tricks

Journal of Applied Physiology ◽

10.1152/japplphysiol.00418.2017 ◽

2017 ◽

Vol 123 (2) ◽

pp. 460-472 ◽

Cited By ~ 9

Author(s):

Scott K. Powers

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Cardiac Myocytes ◽

Endurance Exercise ◽

Ischemia Reperfusion ◽

Muscle Fibers ◽

Cardiac Phenotype ◽

Endurance Exercise Training ◽

Skeletal Muscle Fibers ◽

Endurance exercise training promotes numerous cellular adaptations in both cardiac myocytes and skeletal muscle fibers. For example, exercise training fosters changes in mitochondrial function due to increased mitochondrial protein expression and accelerated mitochondrial turnover. Additionally, endurance exercise training alters the abundance of numerous cytosolic and mitochondrial proteins in both cardiac and skeletal muscle myocytes, resulting in a protective phenotype in the active fibers; this exercise-induced protection of cardiac and skeletal muscle fibers is often referred to as “exercise preconditioning.” As few as 3–5 consecutive days of endurance exercise training result in a preconditioned cardiac phenotype that is sheltered against ischemia-reperfusion-induced injury. Similarly, endurance exercise training results in preconditioned skeletal muscle fibers that are resistant to a variety of stresses (e.g., heat stress, exercise-induced oxidative stress, and inactivity-induced atrophy). Many studies have probed the mechanisms responsible for exercise-induced preconditioning of cardiac and skeletal muscle fibers; these studies are important, because they provide an improved understanding of the biochemical mechanisms responsible for exercise-induced preconditioning, which has the potential to lead to innovative pharmacological therapies aimed at minimizing stress-induced injury to cardiac and skeletal muscle. This review summarizes the development of exercise-induced protection of cardiac myocytes and skeletal muscle fibers and highlights the putative mechanisms responsible for exercise-induced protection in the heart and skeletal muscles.

The Importance of Fatty Acids as Nutrients during Post-Exercise Recovery

Nutrients ◽

10.3390/nu12020280 ◽

2020 ◽

Vol 12 (2) ◽

pp. 280 ◽

Cited By ~ 7

Author(s):

Anne-Marie Lundsgaard ◽

Andreas M. Fritzen ◽

Bente Kiens

Keyword(s):

Skeletal Muscle ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Whole Body ◽

Tissue Blood Flow ◽

Peroxisome Proliferator ◽

Early Recovery ◽

Peroxisome Proliferator Activated Receptor ◽

Post Exercise ◽

It is well recognized that whole-body fatty acid (FA) oxidation remains increased for several hours following aerobic endurance exercise, even despite carbohydrate intake. However, the mechanisms involved herein have hitherto not been subject to a thorough evaluation. In immediate and early recovery (0–4 h), plasma FA availability is high, which seems mainly to be a result of hormonal factors and increased adipose tissue blood flow. The increased circulating availability of adipose-derived FA, coupled with FA from lipoprotein lipase (LPL)-derived very-low density lipoprotein (VLDL)-triacylglycerol (TG) hydrolysis in skeletal muscle capillaries and hydrolysis of TG within the muscle together act as substrates for the increased mitochondrial FA oxidation post-exercise. Within the skeletal muscle cells, increased reliance on FA oxidation likely results from enhanced FA uptake into the mitochondria through the carnitine palmitoyltransferase (CPT) 1 reaction, and concomitant AMP-activated protein kinase (AMPK)-mediated pyruvate dehydrogenase (PDH) inhibition of glucose oxidation. Together this allows glucose taken up by the skeletal muscles to be directed towards the resynthesis of glycogen. Besides being oxidized, FAs also seem to be crucial signaling molecules for peroxisome proliferator-activated receptor (PPAR) signaling post-exercise, and thus for induction of the exercise-induced FA oxidative gene adaptation program in skeletal muscle following exercise. Collectively, a high FA turnover in recovery seems essential to regain whole-body substrate homeostasis.

Exercise training promotes a GDF15-associated reduction in fat mass in older adults with obesity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00439.2018 ◽

2019 ◽

Vol 316 (5) ◽

pp. E829-E836 ◽

Cited By ~ 4

Author(s):

Hui Zhang ◽

Ciarán E. Fealy ◽

John P. Kirwan

Keyword(s):

Exercise Training ◽

Fat Mass ◽

Animal Studies ◽

Acute Exercise ◽

Exercise Intervention ◽

Resting Energy Expenditure ◽

Human Obesity ◽

Total Fat ◽

Exercise Induced ◽

Obesity is a major risk factor for metabolic disease. Growth differentiation factor 15 (GDF15) has shown promise as a weight loss agent for obesity in animal studies. In healthy lean humans, fasting plasma GDF15 increases after acute exercise. However, the role of GDF15 in human obesity and the response of plasma GDF15 to exercise training in patients with obesity is unknown. Here, 24 sedentary volunteers with obesity [age: 65 ± 1 yr; body mass index (BMI): 35.3 ± 0.9 kg/m2] participated in a supervised 12-wk aerobic exercise intervention: 1 h/day, 5 days/wk at ~85% maximum heart rate with controlled isocaloric diet. As a result, plasma GDF15 was significantly increased (PRE: 644.1 ± 42.6 pg/ml, POST: 704.4 ± 47.2 pg/ml, P < 0.01) after the exercise intervention. Inconsistent with animal models, ΔGDF15 was not correlated with change in weight, BMI, or resting energy expenditure. However, ΔGDF15 was correlated with a reduction in total fat mass ( P < 0.05), abdominal fat mass ( P < 0.05), and android fat mass ( P ≤ 0.05). Participants with a positive GDF15 response to exercise had increased total fat oxidation (PRE: 0.25 ± 0.05 mg·kg−1·min−1, POST: 0.43 ± 0.07 mg·kg−1·min−1, P ≤ 0.05), metabolic flexibility [PRE: −0.01 ± 0.01 delta respiratory quotient (RQ), POST: 0.06 ± 0.01 delta RQ, P < 0.001], and insulin sensitivity (PRE: 0.33 ± 0.01 QUICKI index, POST: 0.34 ± 0.01 QUICKI index, P < 0.01), suggesting a link between GDF15 and fat mass loss as well as exercise-induced metabolic improvement in humans with obesity. We conclude that the exercise-induced increase in plasma GDF15 and the association with reduced fat mass may indicate a role for GDF15 as a therapeutic target for human obesity.