scholarly journals Melatonin attenuates mitochondrial and metabolic dysfunction caused by leptin deficiency

2018 ◽  
Author(s):  
Yaiza Potes ◽  
Andrea Díaz-Luis ◽  
Juan C Bermejo-Millo ◽  
Zulema Pérez-Martínez ◽  
Beatriz de Luxán-Delgado ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Energy Production ◽  
Energy Homeostasis ◽  
Nutrient Sensing ◽  
Type I ◽  
Metabolic Dysfunction ◽  
Deficient Animal ◽  
Melatonin Treatment ◽  
Leptin Deficiency ◽  
Type Ii Fibers

AbstractLeptin, as a nutritional inhibitor by repressing food intake, is critical compromised in the major common forms of obesity. Skeletal muscle is the main effector tissue for energy expenditure modifications by the effect of endocrine axes, such as leptin signaling. Our study has been carried out using skeletal muscle from leptin-deficient animal model, in order to ascertain the importance of this hormone in eating disorders. Here we report that leptin-deficiency stimulates an uncontrolled oxidative phosphorylation metabolism, resulting in an excess of energy production that culminates in mitochondrial dysfunction. Thus, different nutrient sensing pathways are perturbed, loosing proteostasis and promoting lipid anabolism, that induces myofiber degeneration and drives oxidative type I fiber conversion. Melatonin treatment plays a significant role in regulating energy homeostasis and fuel utilization. This study reveals melatonin to be a decisive mitochondrial function-fate regulator, with implications for resembling physiological energy requirements and targeting glycolytic type II fibers recovery.

Regulation of skeletal muscle energy/nutrient-sensing pathways during metabolic adaptation to fasting in healthy humans

2014 ◽  
Vol 307 (10) ◽  
pp. E885-E895 ◽  
Author(s):  
Marjolein A. Wijngaarden ◽  
Leontine E. H. Bakker ◽  
Gerard C. van der Zon ◽  
Peter A. C. 't Hoen ◽  
Ko Willems van Dijk ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Lipid Oxidation ◽  
Energy Homeostasis ◽  
Nutrient Sensing ◽  
Whole Body ◽  
Metabolic Adaptation ◽  
Protein Kinase Activity ◽  
Short Term ◽  
Muscle Energy

During fasting, rapid metabolic adaptations are required to maintain energy homeostasis. This occurs by a coordinated regulation of energy/nutrient-sensing pathways leading to transcriptional activation and repression of specific sets of genes. The aim of the study was to investigate how short-term fasting affects whole body energy homeostasis and skeletal muscle energy/nutrient-sensing pathways and transcriptome in humans. For this purpose, 12 young healthy men were studied during a 24-h fast. Whole body glucose/lipid oxidation rates were determined by indirect calorimetry, and blood and skeletal muscle biopsies were collected and analyzed at baseline and after 10 and 24 h of fasting. As expected, fasting induced a time-dependent decrease in plasma insulin and leptin levels, whereas levels of ketone bodies and free fatty acids increased. This was associated with a metabolic shift from glucose toward lipid oxidation. At the molecular level, activation of the protein kinase B (PKB/Akt) and mammalian target of rapamycin pathways was time-dependently reduced in skeletal muscle during fasting, whereas the AMP-activated protein kinase activity remained unaffected. Furthermore, we report some changes in the phosphorylation and/or content of forkhead protein 1, sirtuin 1, and class IIa histone deacetylase 4, suggesting that these pathways might be involved in the transcriptional adaptation to fasting. Finally, transcriptome profiling identified genes that were significantly regulated by fasting in skeletal muscle at both early and late time points. Collectively, our study provides a comprehensive map of the main energy/nutrient-sensing pathways and transcriptomic changes during short-term adaptation to fasting in human skeletal muscle.

Muscle Biopsy Samples for Histochemical Processing: Alterations Induced by Storage

1988 ◽  
Vol 25 (1) ◽  
pp. 77-82 ◽  
Author(s):  
K. G. Braund ◽  
K. A. Amling
Keyword(s):  
Skeletal Muscle ◽  
Cell Morphology ◽  
Type I ◽  
Type Ii ◽  
Tissue Samples ◽  
Frozen Tissue ◽  
Fresh Frozen ◽  
Healthy Dogs ◽  
Morphology And Morphometry ◽  
Type Ii Fibers

Skeletal muscle samples from two healthy dogs were stored in ice at 0 C for up to 30 hours to examine the influence of time on cell morphology and morphometry. Cytochemical and histochemical properties of muscle to 18 hours were not markedly different from fresh frozen tissue. Samples stored to 30 hours were still satisfactory, despite a decline and unevenness in depth of staining. Morphometry from samples stored at 0 C for 6 hours or longer is not recommended, due to the statistically significant increase in diameter (from 21 to 25%) of type I and type II fibers.

scholarly journals Differential regulation of the fiber type-specific gene expression of the sarcoplasmic reticulum calcium-ATPase isoforms induced by exercise training

2014 ◽  
Vol 117 (5) ◽  
pp. 544-555 ◽  
Author(s):  
Marc P. Morissette ◽  
Shanel E. Susser ◽  
Andrew N. Stammers ◽  
Kimberley A. O'Hara ◽  
Phillip F. Gardiner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Exercise Training ◽  
Calcium Atpase ◽  
Specific Gene ◽  
Type I ◽  
Fiber Types ◽  
Type Ii ◽  
Type Ii Fibers ◽  
Sarcoplasmic Reticulum Calcium

The regulatory role of adenosine monophosphate-activated protein kinase (AMPK)-α2 on sarcoplasmic reticulum calcium-ATPase (SERCA) 1a and SERCA2a in different skeletal muscle fiber types has yet to be elucidated. Sedentary (Sed) or exercise-trained (Ex) wild-type (WT) and AMPKα2-kinase dead (KD) transgenic mice, which overexpress a mutated and inactivated AMPKα2 subunit, were utilized to characterize how genotype or exercise training influenced the regulation of SERCA isoforms in gastrocnemius. As expected, both Sed and Ex KD mice had >40% lower AMPK phosphorylation and 30% lower SERCA1a protein than WT mice ( P < 0.05). In contrast, SERCA2a protein was not different among KD and WT mice. Exercise increased SERCA1a and SERCA2a protein content among WT and KD mice, compared with their Sed counterparts. Maximal SERCA activity was lower in KD mice, compared with WT. Total phospholamban protein was higher in KD mice than in WT and lower in Ex compared with Sed mice. Exercise training increased phospholamban Ser16 phosphorylation in WT mice. Laser capture microdissection and quantitative PCR indicated that SERCA1a mRNA expression among type I fibers was not altered by genotype or exercise, but SERCA2a mRNA was increased 30-fold in WT+Ex, compared with WT+Sed. In contrast, the exercise-stimulated increase for SERCA2a mRNA was blunted in KD mice. Exercise upregulated SERCA1a and SERCA2a mRNA among type II fibers, but was not altered by genotype. Collectively, these data suggest that exercise differentially influences SERCA isoform expression in type I and type II fibers. Additionally, AMPKα2 influences the regulation of SERCA2a mRNA in type I skeletal muscle fibers following exercise training.

scholarly journals Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderly

2007 ◽  
Vol 292 (1) ◽  
pp. E151-E157 ◽  
Author(s):  
Lex B. Verdijk ◽  
René Koopman ◽  
Gert Schaart ◽  
Kenneth Meijer ◽  
Hans H. C. M. Savelberg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Fiber Type ◽  
The Elderly ◽  
Type I ◽  
Type Ii ◽  
Fiber Area ◽  
Muscle Fiber Atrophy ◽  
Fiber Atrophy ◽  
Type Ii Fibers

Satellite cells (SC) are essential for skeletal muscle growth and repair. Because sarcopenia is associated with type II muscle fiber atrophy, we hypothesized that SC content is specifically reduced in the type II fibers in the elderly. A total of eight elderly (E; 76 ± 1 yr) and eight young (Y; 20 ± 1 yr) healthy males were selected. Muscle biopsies were collected from the vastus lateralis in both legs. ATPase staining and a pax7-antibody were used to determine fiber type-specific SC content (i.e., pax7-positive SC) on serial muscle cross sections. In contrast to the type I fibers, the proportion and mean cross-sectional area of the type II fibers were substantially reduced in E vs. Y. The number of SC per type I fiber was similar in E and Y. However, the number of SC per type II fiber was substantially lower in E vs. Y (0.044 ± 0.003 vs. 0.080 ± 0.007; P < 0.01). In addition, in the type II fibers, the number of SC relative to the total number of nuclei and the number of SC per fiber area were also significantly lower in E. This study is the first to show type II fiber atrophy in the elderly to be associated with a fiber type-specific decline in SC content. The latter is evident when SC content is expressed per fiber or per fiber area. The decline in SC content might be an important factor in the etiology of type II muscle fiber atrophy, which accompanies the loss of skeletal muscle with aging.

scholarly journals Functional and structural adaptations of skeletal muscle to microgravity

2001 ◽  
Vol 204 (18) ◽  
pp. 3201-3208 ◽  
Author(s):  
Robert H. Fitts ◽  
Danny R. Riley ◽  
Jeffrey J. Widrick
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Peak Force ◽  
Type I ◽  
Type Ii ◽  
Shortening Velocity ◽  
Slow Type ◽  
Fiber Atrophy ◽  
Type I Fibers ◽  
Type Ii Fibers

SUMMARY Our purpose is to summarize the major effects of space travel on skeletal muscle with particular emphasis on factors that alter function. The primary deleterious changes are muscle atrophy and the associated decline in peak force and power. Studies on both rats and humans demonstrate a rapid loss of cell mass with microgravity. In rats, a reduction in muscle mass of up to 37% was observed within 1 week. For both species, the antigravity soleus muscle showed greater atrophy than the fast-twitch gastrocnemius. However, in the rat, the slow type I fibers atrophied more than the fast type II fibers, while in humans, the fast type II fibers were at least as susceptible to space-induced atrophy as the slow fiber type. Space flight also resulted in a significant decline in peak force. For example, the maximal voluntary contraction of the human plantar flexor muscles declined by 20–48% following 6 months in space, while a 21% decline in the peak force of the soleus type I fibers was observed after a 17-day shuttle flight. The reduced force can be attributed both to muscle atrophy and to a selective loss of contractile protein. The former was the primary cause because, when force was expressed per cross-sectional area (kNm−2), the human fast type II and slow type I fibers of the soleus showed no change and a 4% decrease in force, respectively. Microgravity has been shown to increase the shortening velocity of the plantar flexors. This increase can be attributed both to an elevated maximal shortening velocity (V0) of the individual slow and fast fibers and to an increased expression of fibers containing fast myosin. Although the cause of the former is unknown, it might result from the selective loss of the thin filament actin and an associated decline in the internal drag during cross-bridge cycling. Despite the increase in fiber V0, peak power of the slow type I fiber was reduced following space flight. The decreased power was a direct result of the reduced force caused by the fiber atrophy. In addition to fiber atrophy and the loss of force and power, weightlessness reduces the ability of the slow soleus to oxidize fats and increases the utilization of muscle glycogen, at least in rats. This substrate change leads to an increased rate of fatigue. Finally, with return to the 1g environment of earth, rat studies have shown an increased occurrence of eccentric contraction-induced fiber damage. The damage occurs with re-loading and not in-flight, but the etiology has not been established.

The Effects of Non-Weight Bearing on Skeletal Muscle in Older Rats: an Interrupted Bout versus an Uninterrupted Bout

2004 ◽  
Vol 5 (3) ◽  
pp. 195-202 ◽  
Author(s):  
Alissa Guildner Gehrke ◽  
Margaret Sheie Krull ◽  
Robin Shotwell McDonald ◽  
Tracy Sparby ◽  
Jessica Thoele ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Weight Bearing ◽  
Cross Sectional Area ◽  
Type I ◽  
Type Ii ◽  
Sectional Area ◽  
Cross Sectional ◽  
Age Related ◽  
Type Ii Fibers

Age-related changes in skeletal muscle, in combination with bed rest, may result in a poorer rehabilitation potential for an elderly patient. The purpose of this study was to determine the effects of non-weight bearing (hind limb unweighting [HU]) on the soleus and extensor digitorum longus (EDL) in older rats. Two non-weight bearing conditions were used: an uninterrupted bout of HU and an interrupted bout of HU. Twenty-one rats were randomly placed into 1 of 3 groups: control, interrupted HU (2 phases of 7 days of HU, separated by a 4-day weight-bearing phase) and an uninterrupted HU (18 uninterrupted days of HU). Following non-weight bearing, the soleus and EDL muscles were removed. Fiber type identification was performed by myofibrillar ATPase and cross-sectional area was determined. The findings suggest that any period of non-weight bearing leads to a decrease in muscle wet weight (19%-45%). Both type I and type II fibers of the soleus showed atrophy (decrease in cross-sectional area, 35%-44%) with an uninterrupted bout of non-weight bearing. Only the type II fibers of the soleus showed recovery with an interrupted bout of weight bearing. In the EDL, type II fibers were more affected by an uninterrupted bout of non-weight bearing (15% decrease in fiber size) compared to the type I fibers. EDL type II fibers showed more atrophy with interrupted bouts of non-weight bearing than with a single bout (a 40% compared to a 15% decrease). This study shows that initial weight bearing after an episode of non-weight bearing may be damaging to type II fibers of the EDL.

Effects of carnosine on contractile apparatus Ca2+ sensitivity and sarcoplasmic reticulum Ca2+ release in human skeletal muscle fibers

2012 ◽  
Vol 112 (5) ◽  
pp. 728-736 ◽  
Author(s):  
T. L. Dutka ◽  
C. R. Lamboley ◽  
M. J. McKenna ◽  
R. M. Murphy ◽  
G. D. Lamb
Keyword(s):  
Skeletal Muscle ◽  
Human Muscle ◽  
Muscle Performance ◽  
Type I ◽  
Type Ii ◽  
Contractile Apparatus ◽  
Muscle Carnosine ◽  
Ec Coupling ◽  
Type I Fibers ◽  
Type Ii Fibers

There is considerable interest in potential ergogenic and therapeutic effects of increasing skeletal muscle carnosine content, although its effects on excitation-contraction (EC) coupling in human muscle have not been defined. Consequently, we sought to characterize what effects carnosine, at levels attained by supplementation, has on human muscle fiber function, using a preparation with all key EC coupling proteins in their in situ positions. Fiber segments, obtained from vastus lateralis muscle of human subjects by needle biopsy, were mechanically skinned, and their Ca2+ release and contractile apparatus properties were characterized. Ca2+ sensitivity of the contractile apparatus was significantly increased by 8 and 16 mM carnosine (increase in pCa50 of 0.073 ± 0.007 and 0.116 ± 0.006 pCa units, respectively, in six type I fibers, and 0.063 ± 0.018 and 0.103 ± 0.013 pCa units, respectively, in five type II fibers). Caffeine-induced force responses were potentiated by 8 mM carnosine in both type I and II fibers, with the potentiation in type II fibers being entirely explicable by the increase in Ca2+ sensitivity of the contractile apparatus caused by carnosine. However, the potentiation of caffeine-induced responses caused by carnosine in type I fibers was beyond that expected from the associated increase in Ca2+ sensitivity of the contractile apparatus and suggestive of increased Ca2+-induced Ca2+ release. Thus increasing muscle carnosine content likely confers benefits to muscle performance in both fiber types by increasing the Ca2+ sensitivity of the contractile apparatus and possibly also by aiding Ca2+ release in type I fibers, helping to lessen or slow the decline in muscle performance during fatiguing stimulation.

Effects of fiber type and training on beta-adrenoceptor density in human skeletal muscle

1989 ◽  
Vol 257 (5) ◽  
pp. E736-E742 ◽  
Author(s):  
W. H. Martin ◽  
A. R. Coggan ◽  
R. J. Spina ◽  
J. E. Saffitz
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Fiber Type ◽  
Type I ◽  
Type Ii ◽  
Receptor Density ◽  
Beta Receptor ◽  
Type I Fibers ◽  
Total Tissue ◽  
Type Ii Fibers

The density and distribution of beta-adrenergic receptors in type I and II fibers of human gastrocnemius and quadriceps muscles were characterized in ten healthy sedentary subjects and in a subgroup of six subjects before and after 12 wk of endurance exercise training. Total tissue content of beta-receptors was measured in frozen sections of skeletal muscle biopsies incubated with 125I-labeled cyanopindolol in the presence and absence of 10(-5) M L-propranolol. The relative beta-receptor densities of type I and II fibers were delineated autoradiographically. Muscle fiber types were identified in adjacent serial sections by histochemical staining of myofibrillar adenosine-triphosphatase (ATPase) activity. Type I fibers had a threefold greater beta-receptor density than type II fibers of the same muscle [P less than 0.001; type I-to-type II fiber ratio of beta-receptor density was 3.06 +/- 0.43 (SD)]. Exercise training elicited a change in muscle fiber subtype composition (+34% type IIa and -42% type IIb; P less than 0.05 and P = 0.066, respectively), a 40% increase in citrate synthase activity of skeletal muscle (P = 0.01), and a 23% rise in peak oxygen uptake (P less than 0.001). However, no change in total tissue content of beta-receptors was observed after exercise training, even when receptor density was adjusted for preconditioning fiber type composition. Thus beta-receptor density of type I fibers of human skeletal muscle is threefold greater than that of type II fibers. Enhanced capacity for aerobic metabolism after endurance exercise training is not associated with upregulation of total beta-receptor density.

scholarly journals Phosphorylation of αB-crystallin and its cytoskeleton association differs in skeletal myofiber types depending on resistance exercise intensity and volume

2019 ◽  
Vol 126 (6) ◽  
pp. 1607-1618 ◽  
Author(s):  
Daniel Jacko ◽  
Käthe Bersiner ◽  
Jonas Hebchen ◽  
Markus de Marées ◽  
Wilhelm Bloch ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Resistance Exercise ◽  
Mechanical Stress ◽  
Fiber Type ◽  
Type I ◽  
Type Ii ◽  
Αb Crystallin ◽  
Serine 59 ◽  
Type I Fibers ◽  
Type Ii Fibers

αB-crystallin (CRYAB) is an important actor in the immediate cell stabilizing response following mechanical stress in skeletal muscle. Yet, only little is known regarding myofiber type-specific stress responses of CRYAB. We investigated whether the phosphorylation of CRYAB at serine 59 (pCRYABSer59) and its cytoskeleton association are influenced by varying load-intensity and -volume in a fiber type-specific manner. Male subjects were assigned to 1, 5, and 10 sets of different acute resistance exercise protocols: hypertrophy (HYP), maximum strength (MAX), strength endurance (SE), low intensity (LI), and three sets of maximum eccentric resistance exercise (ECC). Skeletal muscle biopsies were taken at baseline and 30 min after exercise. Western blot revealed an increase inpCRYABSer59only following 5 and 10 sets in groups HYP, MAX, SE, and LI as well as following 3 sets in the ECC group. In type I fibers, immunohistochemistry determined increasedpCRYABSer59in all groups. In type II fibers,pCRYABSer59only increased in MAX and ECC groups, with the increase in type II fibers exceeding that of type I fibers in ECC. Association of CRYAB andpCRYABSer59with the cytoskeleton reflected the fiber type-specific phosphorylation pattern. Phosphorylation of CRYAB and its association with the cytoskeleton in type I and II myofibers is highly specific in terms of loading intensity and volume. Most likely, this is based on specific recruitment patterns of the different myofiber entities due to the different resistance exercise loadings. We conclude thatpCRYABSer59indicates contraction-induced mechanical stress exposure of single myofibers in consequence of resistance exercise.NEW & NOTEWORTHY We determined that the phosphorylation of αB-crystallin at serine 59 (pCRYABSer59) after resistance exercise differs between myofiber types in a load- and intensity-dependent manner. The determination ofpCRYABSer59could serve as a marker indirectly indicating contractile involvement and applied mechanical stress on individual fibers. By that, it is possible to retrospectively assess the impact of resistance exercise loading on skeletal muscle fiber entities.

scholarly journals Dissociation between short-term unloading and resistance training effects on skeletal muscle Na+,K+-ATPase, muscle function, and fatigue in humans

2016 ◽  
Vol 121 (5) ◽  
pp. 1074-1086 ◽  
Author(s):  
Ben D. Perry ◽  
Victoria L. Wyckelsma ◽  
Robyn M. Murphy ◽  
Collene H. Steward ◽  
Mitchell Anderson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Muscle Function ◽  
Fiber Type ◽  
Peak Torque ◽  
Quadriceps Muscle ◽  
Type I ◽  
Type Ii ◽  
Type I Fibers ◽  
Type Ii Fibers

Physical training increases skeletal muscle Na+,K+-ATPase content (NKA) and improves exercise performance, but the effects of inactivity per se on NKA content and isoform abundance in human muscle are unknown. We investigated the effects of 23-day unilateral lower limb suspension (ULLS) and subsequent 4-wk resistance training (RT) on muscle function and NKA in 6 healthy adults, measuring quadriceps muscle peak torque; fatigue and venous [K+] during intense one-legged cycling exercise; and skeletal muscle NKA content ([3H]ouabain binding) and NKA isoform abundances (immunoblotting) in muscle homogenates (α1-3, β1–2) and in single fibers (α1–3, β1). In the unloaded leg after ULLS, quadriceps peak torque and cycling time to fatigue declined by 22 and 23%, respectively, which were restored with RT. Whole muscle NKA content and homogenate NKA α1–3 and β1–2 isoform abundances were unchanged with ULLS or RT. However, in single muscle fibers, NKA α3 in type I (−66%, P = 0.006) and β1 in type II fibers (−40%, P = 0.016) decreased after ULLS, with other NKA isoforms unchanged. After RT, NKA α1 (79%, P = 0.004) and β1 (35%, P = 0.01) increased in type II fibers, while α2 (76%, P = 0.028) and α3 (142%, P = 0.004) increased in type I fibers compared with post-ULLS. Despite considerably impaired muscle function and earlier fatigue onset, muscle NKA content and homogenate α1 and α2 abundances were unchanged, thus being resilient to inactivity induced by ULLS. Nonetheless, fiber type-specific downregulation with inactivity and upregulation with RT of several NKA isoforms indicate complex regulation of muscle NKA expression in humans.

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