scholarly journals IL-15 Mediates Mitochondrial Activity through a PPARδ-Dependent-PPARα-Independent Mechanism in Skeletal Muscle Cells

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Shantaé M. Thornton ◽  
James E. Krolopp ◽  
Marcia J. Abbott
Keyword(s):  
Skeletal Muscle ◽  
Citrate Synthase ◽  
Metabolic Effects ◽  
Mitochondrial Activity ◽  
Mrna Levels ◽  
Metabolic Processes ◽  
Atp Production ◽  
Positive Effects ◽  
Increase Energy Expenditure ◽  
Interleukin 15

Molecular mediators of metabolic processes, to increase energy expenditure, have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM), termed “myokines,” has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here, we aimed to determine the importance of PPARαand/or PPARδas targets of IL-15 signaling. C2C12 SKM cells were differentiated for 6 days and treated every other day with IL-15 (100 ng/mL), a PPARαinhibitor (GW-6471), a PPARδinhibitor (GSK-3787), or both IL-15 and the inhibitors. IL-15 increased mitochondrial activity and induced PPARα, PPARδ, PGC1α, PGC1β, UCP2, and Nrf1 expression. There was no effect of inhibiting PPARα, in combination with IL-15, on the aforementioned mRNA levels except for PGC1βand Nrf1. However, with PPARδinhibition, IL-15 failed to induce the expression levels of PGC1α, PGC1β, UCP2, and Nrf1. Further, inhibition of PPARδabolished IL-15 induced increases in citrate synthase activity, ATP production, and overall mitochondrial activity. IL-15 had no effects on mitochondrial biogenesis. Our data indicates that PPARδactivity is required for the beneficial metabolic effects of IL-15 signaling in SKM.

T3 increases mitochondrial ATP production in oxidative muscle despite increased expression of UCP2 and -3

2001 ◽  
Vol 280 (5) ◽  
pp. E761-E769 ◽  
Author(s):  
Kevin R. Short ◽  
Jonas Nygren ◽  
Rocco Barazzoni ◽  
James Levine ◽  
K. Sreekumaran Nair
Keyword(s):  
Skeletal Muscle ◽  
Citrate Synthase ◽  
Atp Synthesis ◽  
Nutrient Flux ◽  
Oxidative Enzymes ◽  
Mrna Levels ◽  
Plantaris Muscle ◽  
Atp Production ◽  
Protein Levels ◽  
Different Types

Triiodothyronine (T3) increases O2 and nutrient flux through mitochondria (Mito) of many tissues, but it is unclear whether ATP synthesis is increased, particularly in different types of skeletal muscle, because variable changes in uncoupling proteins (UCP) and enzymes have been reported. Thus Mito ATP production was measured in oxidative and glycolytic muscles, as well as in liver and heart, in rats administered T3 for 14 days. Relative to saline-treated controls, T3 rats had 80, 168, and 62% higher ATP production in soleus muscle, liver, and heart, respectively, as well as higher activities of citrate synthase (CS; 63, 90, 25%) and cytochrome c oxidase (COX; 119, 225, 52%) in the same tissues (all P < 0.01). In plantaris muscle of T3 rats, CS was only slightly higher (17%, P < 0.05) than in controls, and ATP production and COX were unaffected. mRNA levels of COX I and III were 33 and 47% higher in soleus of T3 rats ( P < 0.01), but there were no differences in plantaris. In contrast, UCP2 and -3 mRNAs were 2.5- to 14-fold higher, and protein levels were 3- to 10-fold higher in both plantaris and soleus of the T3 group. We conclude that T3 increases oxidative enzymes and Mito ATP production and Mito-encoded transcripts in oxidative but not glycolytic rodent tissues. Despite large increases in UCP expression, ATP production was enhanced in oxidative tissues and maintained in glycolytic muscle of hyperthyroid rats.

Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins

1989 ◽  
Vol 256 (3) ◽  
pp. R659-R665 ◽  
Author(s):  
Y. Fong ◽  
L. L. Moldawer ◽  
M. Marano ◽  
H. Wei ◽  
A. Barber ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Muscle Protein ◽  
Interleukin 1 ◽  
Metabolic Effects ◽  
Liver Protein ◽  
Mrna Levels ◽  
Skeletal Muscle Protein ◽  
Male Wistar Rats

Macrophage secretory products are suspected to participate in the severe lean tissue wasting related to chronic illness. The protein metabolic effects of chronic, 7-day cachectin/tumor necrosis factor (cachectin) or interleukin 1 alpha (IL-1 alpha) administration in vivo were studied in male Wistar rats that were 1) freely fed, 2) pair fed, 3) total protein and calorie starved, 4) twice daily lipopolysaccharide (LPS) administered, 5) twice daily cachectin administered, and 6) twice daily IL-1 alpha administered. LPS, cachectin, or IL-1 alpha administration produced anorexia; weight loss in these groups was comparable to respective pair-fed animals. However, LPS, cachectin, or IL-1 alpha accelerated peripheral protein wasting while preserving liver protein content, unlike the pattern in the pair-fed or starved animals in which loss of liver proteins and relative preservation of skeletal muscle protein were observed. The decrease in skeletal muscle protein content in LPS- or cytokine-treated animals was associated with coordinate decreases in muscle mRNA levels for the myofibrillar proteins myosin heavy chain, myosin light chain, actin, and in the 18S and 28S subunits of ribosomal RNA. We conclude that chronic exposure to the cytokines, IL-1 alpha or cachectin, can simulate those body and muscle protein changes seen in experimental LPS administration or chronic disease and markedly differ from the pattern of protein redistribution due to caloric restriction.

scholarly journals Sex Differences in the Metabolic Effects of Testosterone in Sheep

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 123-131 ◽  
Author(s):  
Scott D. Clarke ◽  
Iain J. Clarke ◽  
Alexandra Rao ◽  
Michael A. Cowley ◽  
Belinda A. Henry
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Uncoupling Protein ◽  
Specific Effect ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Nonesterified Fatty Acids ◽  
Glucose Levels ◽  
Amp Activated Protein Kinase ◽  
The Brain

Adiposity is regulated in a sexually divergent manner. This is partly due to sex steroids, but the differential effects of androgens in males and females are unclear. We investigated effects of testosterone on energy balance in castrated male (n = 6) and female sheep (n = 4), which received 3 × 200 mg testosterone implants for 2 wk or blank implants (controls). Temperature probes were implanted into retroperitoneal fat and skeletal muscle. Blood samples were taken to measure metabolites and insulin. In males, muscle and fat biopsies were collected to measure uncoupling protein (UCP) mRNA and phosphorylation of AMP-activated protein kinase and Akt. Testosterone did not change food intake in either sex. Temperature in muscle was higher in males than females, and testosterone reduced heat production in males only. In fat, however, temperature was higher in the castrate males compared with females, and there was no effect of testosterone treatment in either sex. Preprandial glucose levels were lower, but nonesterified fatty acids were higher in females compared with males, irrespective of testosterone. In males, the onset of feeding increased UCP1 and UCP3 mRNA levels in skeletal muscle, without an effect of testosterone. During feeding, testosterone reduced glucose levels in males only but did not alter the phosphorylation of AMP-activated protein kinase or Akt in muscle. Thus, testosterone maintains lower muscle and fat temperatures in males but not females. The mechanism underlying this sex-specific effect of testosterone is unknown but may be due to sexual differentiation of the brain centers controlling energy expenditure.

Whole body metabolic effects of prolonged endurance training in combination with erythropoietin treatment in humans: a randomized placebo controlled trial

2013 ◽  
Vol 305 (7) ◽  
pp. E879-E889 ◽  
Author(s):  
Britt Christensen ◽  
Birgitte Nellemann ◽  
Mads S. Larsen ◽  
Line Thams ◽  
Peter Sieljacks ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Endurance Training ◽  
Exercise Capacity ◽  
Uncoupling Protein ◽  
Metabolic Effects ◽  
Whole Body ◽  
Mrna Levels ◽  
Healthy Humans ◽  
Ucp2 Mrna

Erythropoietin (Epo) administration improves aerobic exercise capacity and insulin sensitivity in renal patients and also increases resting energy expenditure (REE). Similar effects are observed in response to endurance training. The aim was to compare the effects of endurance training with erythropoiesis-stimulating agent (ESA) treatment in healthy humans. Thirty-six healthy untrained men were randomized to 10 wk of either: 1) placebo ( n = 9), 2) ESA ( n = 9), 3) endurance training ( n = 10), or 4) ESA and endurance training ( n = 8). In a single-blinded design, ESA/placebo was injected one time weekly. Training consisted of biking for 1 h at 65% of wattmax three times per week. Measurements performed before and after the intervention were as follows: body composition, maximal oxygen uptake, insulin sensitivity, REE, and palmitate turnover. Uncoupling protein 2 (UCP2) mRNA levels were assessed in skeletal muscle. Fat mass decreased after training ( P = 0.003), whereas ESA induced a small but significant increase in intrahepatic fat ( P = 0.025). Serum free fatty acid (FFA) levels and palmitate turnover decreased significantly in response to training, whereas the opposite pattern was found after ESA. REE corrected for lean body mass increased in response to ESA and training, and muscle UCP2 mRNA levels increased after ESA ( P = 0.035). Insulin sensitivity increased only after training ( P = 0.011). In conclusion: 1) insulin sensitivity is not improved after ESA treatment despite improved exercise capacity, 2) the calorigenic effects of ESA may be related to increased UCP2 gene expression in skeletal muscle, and 3) training and ESA exert opposite effects on lipolysis under basal conditions, increased FFA levels and liver fat fraction was observed after ESA treatment.

scholarly journals Endurance Exercise Training Up-Regulates Lipolytic Proteins and Reduces Triglyceride Content in Skeletal Muscle of Obese Subjects

2013 ◽  
Vol 98 (12) ◽  
pp. 4863-4871 ◽  
Author(s):  
Katie Louche ◽  
Pierre-Marie Badin ◽  
Emilie Montastier ◽  
Claire Laurens ◽  
Virginie Bourlier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Protein Expression ◽  
Endurance Exercise ◽  
Oxidative Capacity ◽  
Metabolic Effects ◽  
Gene Identification ◽  
Mrna Levels ◽  
Endurance Exercise Training ◽  
Obese Subjects

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 &lt; .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 &lt; .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.

scholarly journals Adaptation of mitochondrial ATP production in human skeletal muscle to endurance training and detraining

1992 ◽  
Vol 73 (5) ◽  
pp. 2004-2010 ◽  
Author(s):  
R. Wibom ◽  
E. Hultman ◽  
M. Johansson ◽  
K. Matherei ◽  
D. Constantin-Teodosiu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Endurance Training ◽  
Enzyme Activities ◽  
Citrate Synthase ◽  
Mitochondrial Fraction ◽  
Mitochondrial Enzyme ◽  
Atp Production ◽  
Before And After ◽  
Training And Detraining

The adaptation of mitochondrial ATP production rate (MAPR) to training and detraining was evaluated in nine healthy men. Muscle samples (approximately 60 mg) were obtained before and after 6 wk of endurance training and after 3 wk of detraining. MAPR was measured in isolated mitochondria by a bioluminometric method. In addition, the activities of mitochondrial and glycolytic enzymes were determined in skeletal muscle. In response to training, MAPR increased by 70%, with a substrate combination of pyruvate + palmitoyl-L-carnitine + alpha-ketoglutarate + malate, by 50% with only pyruvate + malate, and by 92% with palmitoyl-L-carnitine + malate. With detraining MAPR decreased by 12–28% from the posttraining rate (although not significantly for all substrates). No differences were found when MAPR was related to the protein content in the mitochondrial fraction. The largest increase in mitochondrial enzyme activities induced by training was observed for cytochrome-c oxidase (78%), whereas succinate cytochrome c reductase showed only an 18% increase. The activity of citrate synthase increased by 40% and of glutamate dehydrogenase by 45%. Corresponding changes in maximal O2 uptake were a 9.6% increase by training and a 6.0% reversion after detraining. In conclusion, both MAPR and mitochondrial enzyme activities are shown to increase with endurance training and to decrease with detraining.

Effects of caloric restriction on mitochondrial function and gene transcripts in rat muscle

2002 ◽  
Vol 283 (1) ◽  
pp. E38-E43 ◽  
Author(s):  
R. Sreekumar ◽  
J. Unnikrishnan ◽  
A. Fu ◽  
J. Nygren ◽  
K. R. Short ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Caloric Restriction ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Control Diet ◽  
Radical Scavenging ◽  
Reactive Oxygen ◽  
Male Rats ◽  
Transcript Levels ◽  
Atp Production

Rodent skeletal muscle mitochondrial DNA has been shown to be a potential site of oxidative damage during aging. Caloric restriction (CR) is reported to reduce oxidative stress and prolong life expectancy in rodents. Gene expression profiling and measurement of mitochondrial ATP production capacity were performed in skeletal muscle of male rats after feeding them either a control diet or calorie-restricted diet (60% of control diet) for 36 wk to determine the potential mechanism of the beneficial effects of CR. CR enhanced the transcripts of genes involved in reactive oxygen free radical scavenging function, tissue development, and energy metabolism while decreasing expression of those genes involved in signal transduction, stress response, and structural and contractile proteins. Real-time PCR measurments confirmed the changes in transcript levels of cytochrome- c oxidase III, superoxide dismutase (SOD)1, and SOD2 that were noted by the microarray approach. Mitochondrial ATP production and citrate synthase were unaltered by the dietary changes. We conclude that CR alters transcript levels of several genes in skeletal muscle and that mitochondrial function in skeletal muscle remains unaltered by the dietary intervention. Alterations in transcripts of many genes involved in reactive oxygen scavenging function may contribute to the increase in longevity reported with CR.

scholarly journals PO-048 Effects of royal jelly administration on endurance training-induced mitochondrial adaptations in skeletal muscle

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Yumiko Takahashi ◽  
Kamiyu Hijikata ◽  
Hideo Hatta
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Soleus Muscle ◽  
Royal Jelly ◽  
Citrate Synthase ◽  
Treadmill Running ◽  
Type I ◽  
Mitochondrial Enzymes ◽  
Positive Effects ◽  
Hydroxyacyl Coa Dehydrogenase

Objective In this study, we investigated effect of royal jelly (RJ), which is produced by honey bees to feed to developing larvae and contains various ingredients including protein, carbohydrate, lipids and minerals, on endurance training-induced adaptations in skeletal muscle in ICR mice. Methods Male mice received either RJ (1.0 mg/g body weight) or distilled water for 3 weeks. Mice in the training group performed treadmill running at 20 m/min for 60 min from 30 min after the administration five times a week. Results We found a significant positive main effects of RJ treatment on the weight of tibialis anterior (TA) muscle and gastrocnemius muscle. There was a significant positive main effect of endurance training on the maximum activities of citrate synthase and β-hydroxyacyl CoA dehydrogenase, which are mitochondrial enzymes, in TA and plantaris muscle (type IIb/IIx dominant), while no significant effect of RJ treatment was found. In soleus muscle (about 40% fiber consistent with type I), the maximum activities of citrate synthase and β-hydroxyacyl CoA dehydrogenase were significantly increased by endurance training in the RJ treated group, while no significant effect of endurance training was found in the control group. Conclusions Our results suggest that RJ treatment had positive effects on the induction of mitochondrial adaptation by endurance training in soleus muscle.

scholarly journals Carbon monoxide, skeletal muscle oxidative stress, and mitochondrial biogenesis in humans

2009 ◽  
Vol 297 (1) ◽  
pp. H392-H399 ◽  
Author(s):  
Michael A. Rhodes ◽  
Martha Sue Carraway ◽  
Claude A. Piantadosi ◽  
Crystal M. Reynolds ◽  
Anne D. Cherry ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Carbon Monoxide ◽  
Superoxide Dismutase ◽  
Mitochondrial Biogenesis ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Mtdna Copy Number ◽  
Atpase 6

Given that the physiology of heme oxygenase-1 (HO-1) encompasses mitochondrial biogenesis, we tested the hypothesis that the HO-1 product, carbon monoxide (CO), activates mitochondrial biogenesis in skeletal muscle and enhances maximal oxygen uptake (V̇o2max) in humans. In 10 healthy subjects, we biopsied the vastus lateralis and performed V̇o2max tests followed by blinded randomization to air or CO breathing (1 h/day at 100 parts/million for 5 days), a contralateral muscle biopsy on day 5, and repeat V̇o2max testing on day 8. Six independent subjects underwent CO breathing and two muscle biopsies without exercise testing. Molecular studies were performed by real-time RT-PCR, Western blot analysis, and immunochemistry. After V̇o2max testing plus CO breathing, significant increases were found in mRNA levels for nuclear respiratory factor-1, peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial transcription factor-A (Tfam), and DNA polymerase γ (Polγ) with no change in mitochondrial DNA (mtDNA) copy number or V̇o2max. Levels of myosin heavy chain I and nuclear-encoded HO-1, superoxide dismutase-2, citrate synthase, mitofusin-1 and -2, and mitochondrial-encoded cytochrome oxidase subunit-I (COX-I) and ATPase-6 proteins increased significantly. None of these responses were reproduced by V̇o2max testing alone, whereas CO alone increased Tfam and Polγ mRNA, and COX-I, ATPase-6, mitofusin-2, HO-1, and superoxide dismutase protein. These findings provide evidence linking the HO/CO response involved in mitochondrial biogenesis in rodents to skeletal muscle in humans through a set of responses involving regulation of the mtDNA transcriptosome and mitochondrial fusion proteins autonomously of changes in exercise capacity.

Muscle fibres: applications for the study of the metabolic consequences of enzyme deficiencies in skeletal muscle

2000 ◽  
Vol 28 (2) ◽  
pp. 159-164 ◽  
Author(s):  
S. Vielhaber ◽  
A. Kudin ◽  
R. Schröder ◽  
C. E. Elger ◽  
W. S. Kunz
Keyword(s):  
Skeletal Muscle ◽  
Large Scale ◽  
Citrate Synthase ◽  
Quantitative Estimation ◽  
Phenotypic Expression ◽  
Metabolic Effects ◽  
Progressive External Ophthalmoplegia ◽  
Muscle Fibres ◽  
Control Analysis ◽  
Mitochondrial Enzymes

Mitochondrial function in saponin-permeabilized muscle fibres can be studied by high-resolution respirometry, laser-excited fluorescence spectroscopy and fluorescence microscopy. We applied these techniques to study metabolic effects of changes in the pattern of mitochondrial enzymes in skeletal muscle of patients with chronic progressive external ophthalmoplegia or Kearns-Sayre syndrome harbouring large-scale deletions of mitchondrial DNA (mtDNA). In all patients combined deficiencies of respiratory chain enzymes containing mitochondrially encoded subunits were observed. The citrate synthase-normalized activity ratios of these enzymes decreased linearly with increasing mtDNA heteroplasmy. This indicates the absence of any well-defined mutation thresholds for mitochondrial enzyme activities in the entire skeletal muscle. We applied metabolic control analysis to perform a quantitative estimation of the metabolic influence of the observed enzyme deficiencies. For patients with degrees of mtDNA heteroplasmy below about 60% we observed at almost normal maximal rates of respiration an increase in flux control coefficients of complexes I and IV. Permeabilized skeletal-muscle fibres of patients with higher degrees of mtDNA heteroplasmy and severe enzyme deficiencies exhibited additionally decreased maximal rates of respiration. This finding indicates the presence of a ‘metabolic threshold’ which can be assessed by functional studies of muscle fibres providing the link to the phenotypic expression of the mtDNA mutation in skeletal muscle.

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