Interleukin-15 as a myokine: mechanistic insight into its effect on skeletal muscle metabolism

2019 ◽  
Vol 44 (3) ◽  
pp. 229-238 ◽  
Author(s):  
Lucien Nadeau ◽  
Céline Aguer
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Muscle Metabolism ◽  
Whole Body ◽  
Soluble Form ◽  
Acid Oxidation ◽  
Α Subunit ◽  
High Doses ◽  
Muscle Energy Metabolism ◽  
Response To Exercise

Interleukin (IL)-15 is a cytokine with important immunological functions. It is highly expressed in skeletal muscle and is believed to be a myokine, a hypothesis supported by the rapid increase in circulating levels of IL-15 in response to exercise. Treatment with high doses of IL-15 results in metabolic adaptations such as improved insulin sensitivity and whole-body fatty acid oxidation and protection from high-fat-diet-induced obesity and insulin resistance. IL-15 secreted by contracting muscle may therefore act as an endocrine factor to improve adiposity and energy metabolism in different tissues. Most studies have used supraphysiological doses of IL-15 that do not represent circulating IL-15 in response to exercise. However, evidence shows that IL-15 levels are higher in muscle interstitium and that IL-15 might improve muscle glucose homeostasis and oxidative metabolism in an autocrine/paracrine manner. Nevertheless, how IL-15 signals in skeletal muscle to improve muscle energy metabolism is not understood completely, especially because the absence of the α subunit of the IL-15 receptor (IL-15Rα) results in a phenotype similar to that of overexpressing/oversecreting IL-15 in mice. In this article, we review the literature to propose a model for the regulation of IL-15 by the soluble form of IL-15Rα to explain why some findings in the literature seem, at first glance, to be contradictory.

scholarly journals MODELING AND SIMULATION OF SKELETAL MUSCLE BASED ON METABOLISM PHYSIOLOGY

2020 ◽  
Vol 20 (09) ◽  
pp. 2040018
Author(s):  
MONAN WANG ◽  
JIALIN HAN ◽  
QIYOU YANG
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Calcium Ion ◽  
Energy Systems ◽  
Metabolic Energy ◽  
Ion Concentration ◽  
Whole Body ◽  
Muscle Energy Metabolism ◽  
Calcium Ion Transport

Skeletal muscle energy metabolism plays a very important role in controlling movement of the whole body and has important theoretical guidance for making exercise training plans and losing weight. In this paper, we developed a mathematical model of skeletal muscle excitation–contraction pathway based on the energy metabolism that links excitation to contraction to explore the effects of different metabolic energy systems on calcium ion changes and the force during skeletal muscle contraction. In this paper, a membrane potential model, a calcium cycle model, a cross-bridge dynamics model and an energy metabolism model were established. Finally, the physiological phenomenon of calcium ion transport and calcium ion concentration change of the sarcoplasm was simulated. The results show that the phosphagen system has the fastest metabolic rate and the phosphagen system has the largest impact on the explosive power of skeletal muscle exercise. The specific characteristics of the three metabolic energy systems supporting skeletal muscle movement in vivo were also analyzed in detail.

scholarly journals Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome

2017 ◽  
Vol 8 (4) ◽  
pp. 535-541 ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Tadashi Suga ◽  
Shingo Takada ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Energy Metabolism ◽  
Aerobic Capacity ◽  
Whole Body ◽  
Muscle Energy ◽  
Muscle Energy Metabolism

scholarly journals Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Mayumi Yamato ◽  
Shingo Takada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Aerobic Capacity ◽  
Plantar Flexion ◽  
Exercise Intolerance ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Systemic Oxidative Stress

AbstractOxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

scholarly journals Skeletal Muscle Metabolism: Origin or Prognostic Factor for Amyotrophic Lateral Sclerosis (ALS) Development?

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1449
Author(s):  
Cyril Quessada ◽  
Alexandra Bouscary ◽  
Frédérique René ◽  
Cristiana Valle ◽  
Alberto Ferri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Muscle Metabolism ◽  
The Body ◽  
Energy Deficit ◽  
Acid Oxidation ◽  
Progression Of Disease ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive and selective loss of motor neurons, amyotrophy and skeletal muscle paralysis usually leading to death due to respiratory failure. While generally considered an intrinsic motor neuron disease, data obtained in recent years, including our own, suggest that motor neuron protection is not sufficient to counter the disease. The dismantling of the neuromuscular junction is closely linked to chronic energy deficit found throughout the body. Metabolic (hypermetabolism and dyslipidemia) and mitochondrial alterations described in patients and murine models of ALS are associated with the development and progression of disease pathology and they appear long before motor neurons die. It is clear that these metabolic changes participate in the pathology of the disease. In this review, we summarize these changes seen throughout the course of the disease, and the subsequent impact of glucose–fatty acid oxidation imbalance on disease progression. We also highlight studies that show that correcting this loss of metabolic flexibility should now be considered a major goal for the treatment of ALS.

AMP kinase is not required for the GLUT4 response to exercise and denervation in skeletal muscle

2004 ◽  
Vol 287 (4) ◽  
pp. E739-E743 ◽  
Author(s):  
Burton F. Holmes ◽  
David B. Lang ◽  
Morris J. Birnbaum ◽  
James Mu ◽  
G. Lynis Dohm
Keyword(s):  
Skeletal Muscle ◽  
Dominant Negative ◽  
Treadmill Running ◽  
Wild Type ◽  
Α Subunit ◽  
Ampk Activity ◽  
Denervated Muscles ◽  
Amp Activated Protein Kinase ◽  
Response To Exercise

An acute bout of exercise increases muscle GLUT4 mRNA in mice, and denervation decreases GLUT4 mRNA. AMP-activated protein kinase (AMPK) activity in skeletal muscle is also increased by exercise, and GLUT4 mRNA is increased in mouse skeletal muscle after treatment with AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside(AICAR). These findings suggest that AMPK activation might be responsible for the increase in GLUT4 mRNA expression in response to exercise. To investigate the role of AMPK in GLUT4 regulation in response to exercise and denervation, transgenic mice with a mutated AMPK α-subunit (dominant negative; AMPK-DN) were studied. GLUT4 did not increase in AMPK-DN mice that were treated with AICAR, demonstrating that muscle AMPK is inactive. Exercise (two 3-h bouts of treadmill running separated by 1 h of rest) increased GLUT4 mRNA in both wild-type and AMPK-DN mice. Likewise, denervation decreased GLUT4 mRNA in both wild-type and AMPK-DN mice. GLUT4 mRNA was also increased by AICAR treatment in both the innervated and denervated muscles. These data demonstrate that AMPK is not required for the response of GLUT4 mRNA to exercise and denervation.

scholarly journals Substrate oxidation in primary human skeletal muscle cells is influenced by donor age

2020 ◽  
Vol 382 (3) ◽  
pp. 599-608
Author(s):  
Vigdis Aas ◽  
G. Hege Thoresen ◽  
Arild C. Rustan ◽  
Jenny Lund
Keyword(s):  
Skeletal Muscle ◽  
Oleic Acid ◽  
Energy Metabolism ◽  
Substrate Oxidation ◽  
Pyruvate Dehydrogenase Kinase ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Donor Age ◽  
Human Myotubes ◽  
Human Skeletal Muscle Cells

AbstractPrimary human myotubes represent an alternative system to intact skeletal muscle for the study of human diseases related to changes in muscle energy metabolism. This work aimed to study if fatty acid and glucose metabolism in human myotubes in vitro were related to muscle of origin, donor gender, age, or body mass index (BMI). Myotubes from a total of 82 donors were established from three different skeletal muscles, i.e., musculus vastus lateralis, musculus obliquus internus abdominis, and musculi interspinales, and cellular energy metabolism was evaluated. Multiple linear regression analyses showed that donor age had a significant effect on glucose and oleic acid oxidation after correcting for gender, BMI, and muscle of origin. Donor BMI was the only significant contributor to cellular oleic acid uptake, whereas cellular glucose uptake did not rely on any of the variables examined. Despite the effect of age on substrate oxidation, cellular mRNA expression of pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PPARGC1A) did not correlate with donor age. In conclusion, donor age significantly impacts substrate oxidation in cultured human myotubes, whereas donor BMI affects cellular oleic acid uptake.

scholarly journals Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity

JCI Insight ◽  
2018 ◽  
Vol 3 (9) ◽  
Author(s):  
Steve Lancel ◽  
Matthijs K.C. Hesselink ◽  
Estelle Woldt ◽  
Yves Rouillé ◽  
Emilie Dorchies ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Endurance Capacity ◽  
Muscle Energy ◽  
Muscle Energy Metabolism

Effects of the Anti-Migraine Drug Sumatriptan on Muscle Energy Metabolism: Relationship to Side-Effects

Cephalalgia ◽  
2000 ◽  
Vol 20 (1) ◽  
pp. 39-44 ◽  
Author(s):  
MD Boska ◽  
KMA Welch ◽  
L Schultz ◽  
J Nelson
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Side Effects ◽  
Kinetic Data ◽  
Oxygen Storage ◽  
Resonance Spectroscopy ◽  
Sumatriptan Succinate ◽  
Muscle Energy ◽  
Creatine Kinase Reaction ◽  
Muscle Energy Metabolism

Sumatriptan succinate (Imitrex) is a 5-HT(5-hydroxytryptamine) agonist used for relief of migraine symptoms. Some individuals experience short-lived side-effects, including heaviness of the limbs, chest heaviness and muscle aches and pains. The effects of this drug on skeletal muscle energy metabolism were studied during short submaximal isometric exercises. We studied ATP flux from anaerobic glycolysis (An Gly), the creatine kinase reaction (CK) and oxidative phosphorylation (Ox Phos) using 31P nuclear magnetic resonance spectroscopy (31P MRS) kinetic data collected during exercise. It was found that side-effects induced acutely by injection of 6 mg sumatriptan succinate s.c. were associated with reduced oxygen storage in peripheral skeletal muscle 5–20 min after injection as demonstrated by a transient reduction in mitochondrial function at end-exercise. These results suggest that mild vasoconstriction in peripheral skeletal muscle is associated with the action of sumatriptan and is likely to be the source of the side-effects experienced by some users. Migraine with aura patients were more susceptible to this effect than migraine without aura patients.

Abstract 13921: Targeting Receptor-Interacting Protein 140 to Modulate Energy Metabolism in the Failing Heart

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tsunehisa Yamamoto ◽  
Elizabeth Pruzinsky ◽  
Kirill Batmanov ◽  
Daniel P Kelly
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Interacting Protein ◽  
Failing Heart ◽  
Metabolic Genes ◽  
Cardiac Energy

The nuclear receptors, peroxisome proliferator-activated receptors (PPARs), estrogen-related receptors (ERRs), and their co-regulator PPARγ coactivator-1α (PGC-1α), control postnatal cardiac mitochondrial biogenesis and energy metabolism. During the development of heart failure (HF), the activity of PGC-1/PPAR/ERR is reduced resulting in diminished capacity for fatty acid oxidation (FAO) and ATP production potentially contributing to an “energy-starved” state that contributes to progression of HF. Receptor-Interacting protein 140 (RIP140) serves as a co-repressor of PGC-1/PPAR/ERR in skeletal muscle and adipose tissue. We hypothesized that RIP140 represses cardiac energy metabolism in the normal and failing heart. Accordingly, we targeted Nrip1 (encoding RIP140) using a muscle creatinine kinase (MCK)-driven Cre recombinase to generate striated muscle-specific RIP140 knockout (msRIP140 KO) mice. msRIP140 KO mice appeared normal at baseline with no difference in survival or cardiac systolic function compared to littermate controls. RNA-sequence analysis demonstrated that the expression of genes involved in a wide array of mitochondrial energy metabolic pathways including FAO, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and branched-chain amino acid (BCAA) degradation pathways were upregulated in msRIP140 KO ventricles, and in msRIP140 KO skeletal muscle. msRIP140 KO mice exhibited significantly less cardiac hypertrophy and diastolic dysfunction in response to chronic pressure overload. Next, cardiac-specific (cs) RIP140 KO mice were generated and subjected to transverse aortic constriction/apical myocardial infarction surgery (TAC/MI), an established HF model. csRIP140 KO mice exhibited less cardiac remodeling and systolic dysfunction compared to littermate controls, along with less downregulation of metabolic genes and induction of cardiac stress ( Nppa and Nppb ) and fibrosis response markers ( Tgfb2 and Col3a1 ). We conclude that RIP140 serves as a global co-repressor of cardiac energy metabolic genes in the adult heart and that modulation of RIP140 activity could prove to be a novel therapeutic approach for HF.

Abstract P247: Gut Microbiota From A Rat Model Of Metabolic Syndrome Lowers Fitness Of High Exercise Capacity Rats (HCR/ Tol ) By Impairing Energy Homeostasis And Increasing Blood Pressure

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Guannan Zhou ◽  
Tao Yang ◽  
Sivarajan Kumarasamy ◽  
Bina Joe ◽  
Lauren G Koch
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Energy Metabolism ◽  
Gut Microbiota ◽  
Exercise Capacity ◽  
Energy Homeostasis ◽  
Current Knowledge ◽  
Strong Predictor ◽  
Whole Body ◽  
Acid Oxidation

Introduction: Low exercise capacity is a strong predictor of cardiovascular disease and overall mortality. Previously we have shown that rats artificially selected for low intrinsic exercise capacity (LCR) have reduced longevity and develop features consistent with metabolic syndrome (MetS) compared to high intrinsic exercise capacity rats (HCR). Current knowledge suggests that gut microbiota is an important contributor for host fitness. Thus, we hypothesized that transferring gut microbiota from LCR rats into inbred high capacity runner (HCR /Tol ) rats would increase risk factors for MetS, including high blood pressure (BP), gain in body weight (BW), and altered resting energy metabolism. Methods: Gut microbiota was depleted in male HCR/ Tol rats (4 mo.) by an antibiotic cocktail given orally (50mg/kg of BW/day) for 5 days, followed by weekly fecal microbiota transfer (FMT) from male LCR or HCR rats (13 mo.) to generate HCR/ Tol -LCR FMT (n = 5) or HCR/ Tol -HCR FMT (n = 6) groups. BW was measured every 4 weeks. At week 11, whole body metabolism was measured by indirect calorimetry (Oxymax, Columbus Instruments). Respiratory Exchange Ratio (RER), Energy Expenditure (EE), glucose and fat oxidation were calculated from oxygen consumption and carbon dioxide release (VO 2 and VCO 2 ). At week 12, BP was measured by tail-cuff method (Kent Scientific) and treadmill exercise test was done at week 13. Results: Compared to HCR/ Tol -HCR FMT , HCR/ Tol -LCR FMT showed a significant gain in BW (7.2% vs 1.9%, P<0.05), elevated systolic BP (147 vs 120 mmHg, P<0.0001), diastolic BP (112 vs 91 mmHg, P<0.01), and mean BP (123 vs 100 mmHg, P<0.001). BP changes in HCR/ Tol -LCR FMT associated with 1) increased VO 2 (355 vs 320 ml/hr, P<0.05), 2) elevated VCO 2 (350 vs 298 ml/hr, P<0.01), 3) increased EE (1.8 vs 1.6 kcal/hr, P<0.01), 4) higher RER (0.96 vs 0.91, P<0.001), 5) higher glucose oxidation (1.36 vs 1.12 g/kg/hr, P<0.001) and 6) reduced fatty acid oxidation (0.09 vs 0.15 g/kg/hr, P<0.01) and a 23% lower exercise capacity. Conclusions: Gut microbiota from LCR rats strongly associated with poor health outcomes, notably elevated BP and impaired energy metabolism. These findings suggest that altered energy homeostasis by microbiota is mechanistically linked to host BP regulation within MetS.

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