SAT0464 Metabolic Effects in Skeletal Muscle of Endurance Exercise in Patients with Polymyositis and Dermatomyositis: A Pilot Study

Context: Skeletal muscle lipase and intramyocellular triglyceride (IMTG) play a role in obesity-related metabolic disorders. Objectives: The aim of the present study was to investigate the impact of 8 weeks of endurance exercise training on IMTG content and lipolytic proteins in obese male subjects. Design and Volunteers: Ten obese subjects completed an 8-week supervised endurance exercise training intervention in which vastus lateralis muscle biopsy samples were collected before and after training. Main Outcome Measures: Clinical characteristics and ex vivo substrate oxidation rates were measured pre- and posttraining. Skeletal muscle lipid content and lipolytic protein expression were also investigated. Results: Our data show that exercise training reduced IMTG content by 42% (P < .01) and increased skeletal muscle oxidative capacity, whereas no change in total diacylglycerol content and glucose oxidation was found. Exercise training up-regulated adipose triglyceride lipase, perilipin (PLIN) 3 protein, and PLIN5 protein contents in skeletal muscle despite no change in mRNA levels. Training also increased hormone sensitive–lipase Ser660 phosphorylation. No significant changes in comparative gene identification 58, G0/G1 switch gene 2, and PLIN2 protein and mRNA levels were observed in response to training. Interestingly, we noted a strong relationship between skeletal muscle comparative gene identification 58 and mitochondrial respiratory chain complex I protein contents at baseline (r = 0.87, P < .0001). Conclusions: Endurance exercise training coordinately up-regulates fat oxidative capacity and lipolytic protein expression in skeletal muscle of obese subjects. This physiological adaptation probably favors fat oxidation and may alleviate the lipotoxic lipid pressure in skeletal muscle. Enhancement of IMTG turnover may be required for the beneficial metabolic effects of exercise in obesity.

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Association between hand muscle thickness and whole-body skeletal muscle mass in healthy adults: a pilot study

Journal of Physical Therapy Science ◽

10.1589/jpts.29.1644 ◽

2017 ◽

Vol 29 (9) ◽

pp. 1644-1648 ◽

Cited By ~ 6

Author(s):

Akio Morimoto ◽

Tadashi Suga ◽

Nobuaki Tottori ◽

Michio Wachi ◽

Jun Misaki ◽

...

Keyword(s):

Skeletal Muscle ◽

Pilot Study ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Thickness ◽

Healthy Adults ◽

Whole Body ◽

Hand Muscle

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Exercise, heat shock proteins and insulin resistance

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0529 ◽

2017 ◽

Vol 373 (1738) ◽

pp. 20160529 ◽

Cited By ~ 19

Author(s):

Ashley E. Archer ◽

Alex T. Von Schulze ◽

Paige C. Geiger

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Heat Shock ◽

Heat Shock Proteins ◽

Metabolic Effects ◽

Diabetic Patients ◽

Alcoholic Fatty Liver ◽

Insulin Resistant ◽

Exercise Induced ◽

Shock Proteins

Best known as chaperones, heat shock proteins (HSPs) also have roles in cell signalling and regulation of metabolism. Rodent studies demonstrate that heat treatment, transgenic overexpression and pharmacological induction of HSP72 prevent high-fat diet-induced glucose intolerance and skeletal muscle insulin resistance. Overexpression of skeletal muscle HSP72 in mice has been shown to increase endurance running capacity nearly twofold and increase mitochondrial content by 50%. A positive correlation between HSP72 mRNA expression and mitochondrial enzyme activity has been observed in human skeletal muscle, and HSP72 expression is markedly decreased in skeletal muscle of insulin resistant and type 2 diabetic patients. In addition, decreased levels of HSP72 correlate with insulin resistance and non-alcoholic fatty liver disease progression in livers from obese patients. These data suggest the targeted induction of HSPs could be a therapeutic approach for preventing metabolic disease by maintaining the body's natural stress response. Exercise elicits a number of metabolic adaptations and is a powerful tool in the prevention and treatment of insulin resistance. Exercise training is also a stimulus for increased HSP expression. Although the underlying mechanism(s) for exercise-induced HSP expression are currently unknown, the HSP response may be critical for the beneficial metabolic effects of exercise. Exercise-induced extracellular HSP release may also contribute to metabolic homeostasis by actively restoring HSP72 content in insulin resistant tissues containing low endogenous levels of HSPs. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

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Retinal and choroidal blood flow variations after an endurance exercise: A real-life pilot study at the Paris Marathon

Journal of Science and Medicine in Sport ◽

10.1016/j.jsams.2021.03.013 ◽

2021 ◽

Author(s):

Martine Mauget-Faÿsse ◽

Nicolas Arej ◽

Morgane Paternoster ◽

Kevin Zuber ◽

Sabine Derrien ◽

...

Keyword(s):

Blood Flow ◽

Pilot Study ◽

Endurance Exercise ◽

Real Life ◽

Choroidal Blood Flow

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Linear Skeletal Muscle Ventricle: A Pilot Study

Artificial Organs ◽

10.1111/j.1525-1594.1996.tb00720.x ◽

2008 ◽

Vol 20 (2) ◽

pp. 156-161 ◽

Cited By ~ 1

Author(s):

Yukihiro Kaneko ◽

Akira Furuse

Keyword(s):

Skeletal Muscle ◽

Pilot Study

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ALY688 elicits adiponectin-mimetic signaling and improves insulin action in skeletal muscle cells

AJP Cell Physiology ◽

10.1152/ajpcell.00603.2020 ◽

2021 ◽

Author(s):

Hye Kyoung Sung ◽

Patricia L. Mitchell ◽

Sean Gross ◽

Andre Marette ◽

Gary Sweeney

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Glucose Uptake ◽

Glucose Transporter ◽

Muscle Cells ◽

Temporal Analysis ◽

Skeletal Muscle Cells ◽

Adiponectin Receptor ◽

Metabolic Effects

Adiponectin is well established to mediate many beneficial metabolic effects, and this has stimulated great interest in development and validation of adiponectin receptor agonists as pharmaceutical tools. This study investigated the effects of ALY688, a peptide-based adiponectin receptor agonist, in rat L6 skeletal muscle cells. ALY688 significantly increased phosphorylation of several adiponectin downstream effectors, including AMPK, ACC and p38MAPK, assessed by immunoblotting and immunofluorescence microscopy. Temporal analysis using cells expressing an Akt biosensor demonstrated that ALY688 enhanced insulin sensitivity. This effect was associated with increased insulin-stimulated Akt and IRS-1 phosphorylation. The functional metabolic significance of these signaling effects was examined by measuring glucose uptake in myoblasts stably overexpressing the glucose transporter GLUT4. ALY688 treatment both increased glucose uptake itself and enhanced insulin-stimulated glucose uptake. In the model of high glucose/high insulin (HGHI)-induced insulin resistant cells, both temporal studies using the Akt biosensor as well as immunoblotting assessing Akt and IRS-1 phosphorylation indicated that ALY688 significantly reduced insulin resistance. Importantly, we observed that ALY688 administration to high-fat high sucrose fed mice also improve glucose handling, validating its efficacy in vivo. In summary, these data indicate that ALY688 activates adiponectin signaling pathways in skeletal muscle, leading to improved insulin sensitivity and beneficial metabolic effects.

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Interaction of CREB and PGC-1α Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes

Cellular Physiology and Biochemistry ◽

10.1159/000494655 ◽

2018 ◽

Vol 50 (4) ◽

pp. 1574-1584 ◽

Cited By ~ 6

Author(s):

Xiu-ying Yang ◽

Margaret C.L. Tse ◽

Xiang Hu ◽

Wei-hua Jia ◽

Guan-hua Du ◽

...

Keyword(s):

Skeletal Muscle ◽

Molecular Mechanisms ◽

Metabolic Effects ◽

Hek293 Cells ◽

Metabolic Phenotype ◽

C2c12 Myotubes ◽

Type Iii ◽

Fibronectin Type Iii ◽

Fibronectin Type Iii Domain ◽

Fibronectin Type

Background/Aims: Fibronectin type III domain-containing protein 5 (FNDC5), also known as irisin, is a myokine secreted from muscle in response to exercise. However, the molecular mechanisms that regulate FNDC5 expression and the functional significance of irisn in skeletal muscle remain unknown. In this study, we explored the potential pathways that induce FNDC5 expression and delineated the metabolic effects of irisin on skeletal muscle. Methods: C2C12 myotubes were treated with drugs at various concentrations and durations. The expression and activation of genes were measured by real-time polymerase chain reaction (qRT-PCR) and Western blotting. Oxidative phosphorylation was quantified by measuring the oxygen consumption rate (OCR). Results: We found that the exercise-mimicking treatment (cAMP, forskolin and isoproterenol) increased Fndc5 expression in C2C12 myotubes. CREB over-expressed C2C12 myotubes displayed higher Fndc5 expression. CREB over-expression also promoted peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) expression. PGC-1α-induced Fndc5 expression was blocked when the dominant negative form of CREB (S133A) was present. PGC-1α mutation (S570A) also decreased Fndc5 expression. Immunoprecipitation showed that overexpressed PGC-1α complexed with CREB in HEK293 cells. C2C12 myotubes treated with forskolin also increased endogenous CREB and PGC-1α binding. Functionally, irisin treatment increased mitochondrial respiration, enhanced ATP production, promoted fatty acid oxidation but decreased glycolysis in myotubes. Conclusion: Our observation indicates that cAMP-mediated PGC-1α/CREB interaction triggers Fndc5 expression, which acts as an autocrine/paracrine to shape the metabolic phenotype of myotubes.

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Skeletal muscle biochemical adaptations to exercise training in miniature swine

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.6.1862 ◽

1997 ◽

Vol 82 (6) ◽

pp. 1862-1868 ◽

Cited By ~ 23

Author(s):

Richard M. McAllister ◽

Brian L. Reiter ◽

John F. Amann ◽

M. Harold Laughlin

Keyword(s):

Skeletal Muscle ◽

Antioxidant Enzymes ◽

Lactate Dehydrogenase ◽

Exercise Training ◽

Endurance Exercise ◽

Oxidative Capacity ◽

Treadmill Running ◽

Miniature Swine ◽

Endurance Exercise Training ◽

Hydroxyacyl Coa Dehydrogenase

McAllister, Richard M., Brian L. Reiter, John F. Amann, and M. Harold Laughlin. Skeletal muscle biochemical adaptations to exercise training in miniature swine. J. Appl. Physiol. 82(6): 1862–1868, 1997.—The primary purpose of this study was to test the hypothesis that endurance exercise training induces increased oxidative capacity in porcine skeletal muscle. To test this hypothesis, female miniature swine were either trained by treadmill running 5 days/wk over 16–20 wk (Trn; n = 35) or pen confined (Sed; n = 33). Myocardial hypertrophy, lower heart rates during submaximal stages of a maximal treadmill running test, and increased running time to exhaustion during that test were indicative of training efficacy. A variety of skeletal muscles were sampled and subsequently assayed for the enzymes citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, and lactate dehydrogenase and for antioxidant enzymes. Fiber type composition of a representative muscle was also determined histochemically. The largest increase in CS activity (62%) was found in the gluteus maximus muscle (Sed, 14.7 ± 1.1 μmol ⋅ min−1 ⋅ g−1; Trn, 23.9 ± 1.0; P < 0.0005). Muscles exhibiting increased CS activity, however, were located primarily in the forelimb; ankle and knee extensor and respiratory muscles were unchanged with training. Only two muscles exhibited higher 3-hydroxyacyl-CoA dehydrogenase activity in Trn compared with Sed. Lactate dehydrogenase activity was unchanged with training, as were activities of antioxidant enzymes. Histochemical analysis of the triceps brachii muscle (long head) revealed lower type IIB fiber numbers in Trn (Sed, 42 ± 6%; Trn, 10 ± 4; P < 0.01) and greater type IID/X fiber numbers (Sed, 11 ± 2; Trn, 22 ± 3; P < 0.025). These findings indicate that porcine skeletal muscle adapts to endurance exercise training in a manner similar to muscle of humans and other animal models, with increased oxidative capacity. Specific muscles exhibiting these adaptations, however, differ between the miniature swine and other species.

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Skeletal muscle mitochondrial protein synthesis and respiration in response to the energetic stress of an ultra-endurance race

Journal of Applied Physiology ◽

10.1152/japplphysiol.00457.2017 ◽

2017 ◽

Vol 123 (6) ◽

pp. 1516-1524 ◽

Cited By ~ 6

Author(s):

Adam R. Konopka ◽

William M. Castor ◽

Christopher A. Wolff ◽

Robert V. Musci ◽

Justin J. Reid ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Endurance Exercise ◽

Mitochondrial Respiration ◽

Endurance Athlete ◽

Control Period ◽

Mitochondrial Protein ◽

Mitochondrial Bioenergetics ◽

Mitochondrial Protein Synthesis ◽

Ultra Endurance

The 2016 Colorado Trail Race (CTR) was an ultra-endurance mountain bike race in which competitors cycled for up to 24 h/day between altitudes of 1,675 and 4,025 m to complete 800 km and 21,000 m of elevation gain. In one athlete, we had the unique opportunity to characterize skeletal muscle protein synthesis and mitochondrial respiration in response to a normal activity control period (CON) and the CTR. We hypothesized that mitochondrial protein synthesis would be elevated and mitochondrial respiration would be maintained during the extreme stresses of the CTR. Titrated and bolus doses of ADP were provided to determine substrate-specific oxidative phosphorylation (OXPHOS) and electron transport system (ETS) capacities in permeabilized muscle fibers via high-resolution respirometry. Protein synthetic rates were determined by daily oral consumption of deuterium oxide (2H2O). The endurance athlete had OXPHOS (226 pmol·s−1·mg tissue−1) and ETS (231 pmol·s−1·mg tissue−1) capacities that rank among the highest published to date in humans. Mitochondrial (3.2-fold), cytoplasmic (2.3-fold), and myofibrillar (1.5-fold) protein synthesis rates were greater during CTR compared with CON. With titrated ADP doses, the apparent Km of ADP, OXPHOS, and ETS increased after the CTR. With provision of ADP boluses after the CTR, the addition of fatty acids (−12 and −14%) mitigated the decline in OXPHOS and ETS capacity during carbohydrate-supported respiration (−26 and −31%). In the face of extreme stresses during the CTR, elevated rates of mitochondrial protein synthesis may contribute to rapid adaptations in mitochondrial bioenergetics. NEW & NOTEWORTHY The mechanisms that maintain skeletal muscle function during extreme stresses remain incompletely understood. In the current study, greater rates of mitochondrial protein synthesis during the energetic demands of ultra-endurance exercise may contribute to rapid adaptations in mitochondrial bioenergetics. The endurance athlete herein achieved mitochondrial respiratory capacities among the highest published for humans. Greater mitochondrial protein synthesis during ultra-endurance exercise may contribute to improved mitochondrial respiration and serve as a mechanism to resist cellular energetic stresses.

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