scholarly journals Obesity-induced discrepancy between contractile and metabolic phenotypes in slow- and fast-twitch skeletal muscles of female obese Zucker rats

2017 ◽  
Vol 123 (1) ◽  
pp. 249-259 ◽  
Author(s):  
Luz M. Acevedo ◽  
Ana I. Raya ◽  
Rafael Ríos ◽  
Escolástico Aguilera-Tejero ◽  
José-Luis L. Rivero

A clear picture of skeletal muscle adaptations to obesity and related comorbidities remains elusive. This study describes fiber-type characteristics (size, proportions, and oxidative enzyme activity) in two typical hindlimb muscles with opposite structure and function in an animal model of genetic obesity. Lesser fiber diameter, fiber-type composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of muscle fiber types were assessed in slow (soleus)- and fast (tibialis cranialis)-twitch muscles of obese Zucker rats and compared with age (16 wk)- and sex (females)-matched lean Zucker rats ( n = 16/group). Muscle mass and lesser fiber diameter were lower in both muscle types of obese compared with lean animals even though body weights were increased in the obese cohort. A faster fiber-type phenotype also occurred in slow- and fast-twitch muscles of obese rats compared with lean rats. These adaptations were accompanied by a significant increment in histochemical succinic dehydrogenase activity of slow-twitch fibers in the soleus muscle and fast-twitch fiber types in the tibialis cranialis muscle. Obesity significantly increased plasma levels of proinflammatory cytokines but did not significantly affect protein levels of peroxisome proliferator-activated receptors PPARγ or PGC1α in either muscle. These data demonstrate that, in female Zucker rats, obesity induces a reduction of muscle mass in which skeletal muscles show a diminished fiber size and a faster and more oxidative phenotype. It was noteworthy that this discrepancy in muscle's contractile and metabolic features was of comparable nature and extent in muscles with different fiber-type composition and antagonist functions. NEW & NOTEWORTHY This study demonstrates a discrepancy between morphological (reduced muscle mass), contractile (shift toward a faster phenotype), and metabolic (increased mitochondrial oxidative enzyme activity) characteristics in skeletal muscles of female Zucker fatty rats. It is noteworthy that this inconsistency was comparable (in nature and extent) in muscles with different structure and function.

1992 ◽  
Vol 73 (1) ◽  
pp. 382-387 ◽  
Author(s):  
J. T. Brozinick ◽  
G. J. Etgen ◽  
B. B. Yaspelkis ◽  
J. L. Ivy

The rates of muscle glucose uptake of lean and obese Zucker rats were assessed via hindlimb perfusion under basal conditions (no insulin), in the presence of a maximal insulin concentration (10 mU/ml), and after electrically stimulated muscle contraction in the absence of insulin. The perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy-D-[3H-(G)]glucose. Glucose uptake rates in the soleus (slow-twitch oxidative fibers), red gastrocnemius (fast-twitch oxidative-glycolytic fibers), and white gastrocnemius (fast-twitch glycolytic fibers) under basal conditions and after electrically stimulated muscle contraction were not significantly different between the lean and obese rats. However, the rate of glucose uptake during insulin stimulation was significantly lower for obese than for lean rats in all three fiber types. Significant correlations were found for insulin-stimulated glucose uptake and glucose transporter protein isoform (GLUT-4) content of soleus, red gastrocnemius, and white gastrocnemius of lean (r = 0.79) and obese (r = 0.65) rats. In contrast, the relationships between contraction-stimulated glucose uptake and muscle GLUT-4 content of lean and obese rats were negligible because of inordinately low contraction-stimulated glucose uptakes by the solei. These results suggest that maximal skeletal muscle glucose uptake of obese Zucker rats is resistant to stimulation by insulin but not to contractile activity. In addition, the relationship between contraction-stimulated glucose uptake and GLUT-4 content appears to be fiber-type specific.


BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Pabodha Hettige ◽  
Uzma Tahir ◽  
Kiisa C. Nishikawa ◽  
Matthew J. Gage

Abstract Background Individual skeletal muscles have evolved to perform specific tasks based on their molecular composition. In general, muscle fibers are characterized as either fast-twitch or slow-twitch based on their myosin heavy chain isoform profiles. This approach made sense in the early days of muscle studies when SDS-PAGE was the primary tool for mapping fiber type. However, Next Generation Sequencing tools permit analysis of the entire muscle transcriptome in a single sample, which allows for more precise characterization of differences among fiber types, including distinguishing between different isoforms of specific proteins. We demonstrate the power of this approach by comparing the differential gene expression patterns of extensor digitorum longus (EDL), psoas, and soleus from mice using high throughput RNA sequencing. Results EDL and psoas are typically classified as fast-twitch muscles based on their myosin expression pattern, while soleus is considered a slow-twitch muscle. The majority of the transcriptomic variability aligns with the fast-twitch and slow-twitch characterization. However, psoas and EDL exhibit unique expression patterns associated with the genes coding for extracellular matrix, myofibril, transcription, translation, striated muscle adaptation, mitochondrion distribution, and metabolism. Furthermore, significant expression differences between psoas and EDL were observed in genes coding for myosin light chain, troponin, tropomyosin isoforms, and several genes encoding the constituents of the Z-disk. Conclusions The observations highlight the intricate molecular nature of skeletal muscles and demonstrate the importance of utilizing transcriptomic information as a tool for skeletal muscle characterization.


2005 ◽  
Vol 25 (15) ◽  
pp. 6629-6638 ◽  
Author(s):  
Misook Oh ◽  
Igor I. Rybkin ◽  
Victoria Copeland ◽  
Michael P. Czubryt ◽  
John M. Shelton ◽  
...  

ABSTRACT Skeletal muscles are a mosaic of slow and fast twitch myofibers. During embryogenesis, patterns of fiber type composition are initiated that change postnatally to meet physiological demand. To examine the role of the protein phosphatase calcineurin in the initiation and maintenance of muscle fiber types, we used a “Flox-ON” approach to obtain muscle-specific overexpression of the modulatory calcineurin-interacting protein 1 (MCIP1/DSCR1), an inhibitor of calcineurin. Myo-Cre transgenic mice with early skeletal muscle-specific expression of Cre recombinase were used to activate the Flox-MCIP1 transgene. Contractile components unique to type 1 slow fibers were absent from skeletal muscle of adult Myo-Cre/Flox-MCIP1 mice, whereas oxidative capacity, myoglobin content, and mitochondrial abundance were unaltered. The soleus muscles of Myo-Cre/Flox-MCIP1 mice fatigued more rapidly than the wild type as a consequence of the replacement of the slow myosin heavy chain MyHC-1 with a fast isoform, MyHC-2A. MyHC-1 expression in Myo-Cre/Flox-MCIP1 embryos and early neonates was normal. These results demonstrate that developmental patterning of slow fibers is independent of calcineurin, while the maintenance of the slow-fiber phenotype in the adult requires calcineurin activity.


2006 ◽  
Vol 291 (3) ◽  
pp. 518-528 ◽  
Author(s):  
M. F. Patterson ◽  
G. M. M. Stephenson ◽  
D. G. Stephenson

Using a single, mechanically skinned fiber approach, we tested the hypothesis that denervation (0 to 50 days) of skeletal muscles that do not overlap in fiber type composition [extensor digitorum longus (EDL) and soleus (SOL) muscles of Long-Evans hooded rats] leads to development of different fiber phenotypes. Denervation (50 day) was accompanied by 1) a marked increase in the proportion of hybrid IIB/D fibers (EDL) and I/IIA fibers (SOL) from 30% to >75% in both muscles, and a corresponding decrease in the proportion of pure fibers expressing only one myosin heavy chain (MHC) isoform; 2) complex muscle- and fiber-type specific changes in sarcoplasmic reticulum Ca2+-loading level at physiological pCa ∼7.1, with EDL fibers displaying more consistent changes than SOL fibers; 3) decrease by ∼50% in specific force of all fiber types; 4) decrease in sensitivity to Ca2+, particularly for SOL fibers (by ∼40%); 5) decrease in the maximum steepness of the force-pCa curves, particularly for the hybrid I/IIA SOL fibers (by ∼35%); and 6) increased occurrence of biphasic behavior with respect to Sr2+activation in SOL fibers, indicating the presence of both slow and fast troponin C isoforms. No fiber types common to the two muscles were detected at any time points ( day 7, 21, and 50) after denervation. The results provide strong evidence that not only neural factors, but also the intrinsic properties of a muscle fiber, influence the structural and functional properties of a particular muscle cell and explain important functional changes induced by denervation at both whole muscle and single cell levels.


1988 ◽  
Vol 254 (6) ◽  
pp. E726-E732 ◽  
Author(s):  
R. J. Zeman ◽  
R. Ludemann ◽  
T. G. Easton ◽  
J. D. Etlinger

Chronic treatment of rats with clenbuterol, a beta 2-receptor agonist (8–12 wk), caused hypertrophy of histochemically identified fast- but not slow-twitch fibers within the soleus, while the mean areas of both fiber types were increased in the extensor digitorum longus (EDL). In contrast, treatment with the beta 2-receptor antagonist, butoxamine, reduced fast-twitch fiber size in both muscles. In the solei and to a lesser extent in the EDLs, the ratio of the number of fast- to slow-twitch fibers was increased by clenbuterol, while the opposite was observed with butoxamine. The muscle fiber hypertrophy observed in the EDL was accompanied by parallel increases in maximal tetanic tension and muscle cross-sectional area, while in the solei, progressive increases in rates of force development and relaxation toward values typical of fast-twitch muscles were also observed. Our results suggest a role of beta 2-receptors in regulating muscle fiber type composition as well as growth.


1988 ◽  
Vol 255 (6) ◽  
pp. G772-G778 ◽  
Author(s):  
J. Krier ◽  
T. Adams ◽  
R. A. Meyer

The contractile properties, morphology, and the distribution of striated muscle fiber types of the external and sphincter (EAS) were determined using axial force measurements, fiber size cross-sectional area measurements, and histochemistry. Electrical stimulation of motor axons in pudendal nerve at supramaximal intensities (10 V, 0.05 ms duration) elicited twitch contractions of EAS. The time to peak force after a single pulse ranged from 37 to 42 ms. The time for relaxation to half-maximal twitch force ranged from 20 to 29 ms. Repetitive stimulation of motor axons (0.1-3.0 Hz) produced potentiation and fatigue of single twitch contractile force, suggesting that the EAS of the cat is comprised predominantly of fast-twitch muscle fibers. Confirmation of skeletal muscle fiber types was determined by histochemistry. Frozen serial cross sections of EAS were incubated to demonstrate succinic dehydrogenase (SDH) and myosin adenosine triphosphatase after alkaline preincubation (pH 10.4). Based on these reactions, muscle fibers were classified as fast glycolytic (FG) (high ATPase, low SDH), fast oxidative-glycolytic (FOG) (high ATPase, high SDH), and slow oxidative (SO) (low ATPase, high SDH). The mean percentage +/- SE of each histochemical type was the following: FG, 73.5 +/- 3.9; FOG, 22.8 +/- 3.7; and SO, 3.7 +/- 0.6. These results indicate that the predominant fiber type for the EAS is FG. The EAS of the cat is considered a nominally fast-twitch muscle.


1988 ◽  
Vol 255 (3) ◽  
pp. E374-E382 ◽  
Author(s):  
W. M. Sherman ◽  
A. L. Katz ◽  
C. L. Cutler ◽  
R. T. Withers ◽  
J. L. Ivy

The purposes of this study were to determine whether the muscle insulin resistance of the obese rat is due to a defect in the glucose transport process and whether the insulin resistance is fiber-type specific. The hindlimbs of fasted, 14-wk-old obese (fa/fa) and lean (fa/?) Zucker rats were perfused with perfusate containing 8 mM glucose and no insulin or 8 mM glucose and either a physiological (0.15 mU/ml), a submaximal (1.50 mU/ml), or a maximal (15.0 mU/ml) insulin concentration. Glucose uptake was determined after which the initial rate of glucose transport was determined using 3-O-methyl-D-glucose (3-OMG). Glucose uptake of the obese rats was depressed by 40, 33, 42, and 47% in the absence of insulin and in the presence of the physiological, submaximal, and maximal insulin concentrations, respectively, when compared with lean littermates. Glucose transport in the absence and in the presence of the three insulin concentrations was significantly lower in the soleus (slow-twitch, oxidative fibers), red quadriceps (fast-twitch, oxidative, glycolytic fibers), and gastrocnemius (mixed fibers) of the obese rats when compared with lean rats. Glucose transport in the white quadriceps (fast-twitch, glycolytic fibers) was significantly lower in the obese rats in the absence of insulin and in the presence of the submaximal and maximal insulin concentrations. The glycogen concentration and the activity of hexokinase were the same and the glycogen synthase activity was higher in the muscles for the obese rats when compared to lean rats.(ABSTRACT TRUNCATED AT 250 WORDS)


2008 ◽  
Vol 33 (2) ◽  
pp. 272-281 ◽  
Author(s):  
Thomas J. Walters ◽  
John F. Kragh ◽  
David G. Baer

This study was designed to determine if previously reported differences in the functional impairment of muscles composed of predominantly different fiber types occurs following extended periods of ischemia. We hypothesized that the soleus (Sol) muscle, a predominantly slow-twitch muscle, would be less vulnerable to tourniquet-induced ischemia–reperfusion than the plantaris (Plant), a predominantly fast-twitch muscle, as determined by the assessment of isometric contractile function. Male Sprague–Dawley rats were assigned to one of the following groups to undergo tourniquet application (TKA) (n = 6/group): 2 h TKA, 2 d recovery; 4 h TKA, 2 d recovery; 2 h TKA, 14 d recovery; or 4 h TKA, 14 d recovery. In situ isometric contractile properties were assessed in the predominantly slow-twitch Sol and the predominantly fast-twitch Plant; the contralateral muscle served as the internal control. At 2 d, muscle contraction could not be elicited via neural stimulation, but muscles did contract with direct stimulation, which indicates neural injury. This condition was resolved by day 14. At this time point, tetanic tension (Po) in the Plant was reduced by 45% and 69% in the 2 and 4 h groups, respectively. Po for the Sol was unaffected in the 2 h group, but was reduced by 30% in the 4 h group. The fatigue resistance of the Plant was increased 2 fold in the 4 h group and was unchanged in all other groups. These results demonstrate that vulnerability to tourniquet-induced ischemia–reperfusion injury is dramatically different with respect to muscle fiber-type composition.


Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 243 ◽  
Author(s):  
Manting Ma ◽  
Bolin Cai ◽  
Liang Jiang ◽  
Bahareldin Ali Abdalla ◽  
Zhenhui Li ◽  
...  

Emerging studies indicate important roles for non-coding RNAs (ncRNAs) as essential regulators in myogenesis, but relatively less is known about their function. In our previous study, we found that lncRNA-Six1 can regulate Six1 in cis to participate in myogenesis. Here, we studied a microRNA (miRNA) that is specifically expressed in chickens (miR-1611). Interestingly, miR-1611 was found to contain potential binding sites for both lncRNA-Six1 and Six1, and it can interact with lncRNA-Six1 to regulate Six1 expression. Overexpression of miR-1611 represses the proliferation and differentiation of myoblasts. Moreover, miR-1611 is highly expressed in slow-twitch fibers, and it drives the transformation of fast-twitch muscle fibers to slow-twitch muscle fibers. Together, these data demonstrate that miR-1611 can mediate the regulation of Six1 by lncRNA-Six1, thereby affecting proliferation and differentiation of myoblasts and transformation of muscle fiber types.


1987 ◽  
Vol 63 (5) ◽  
pp. 2101-2110 ◽  
Author(s):  
R. W. Tsika ◽  
R. E. Herrick ◽  
K. M. Baldwin

Three adult skeletal muscle sarcomeric myosin heavy chain (MHC) genes have been identified in the rat, suggesting that the expressed native myosin isoforms can be differentiated, in part, on the basis of their MHC composition. This study was undertaken to ascertain whether the five major native isomyosins [3 fast (Fm1, Fm2, Fm3), 1 slow (Sm), and 1 intermediate (Im)], typically expressed in the spectrum of adult rat skeletal muscles comprising the hindlimb, could be further differentiated on the basis of their MHC profiles in addition to their light chain composition. Results show that in muscles comprised exclusively of fast-twitch glycolytic (FG) fibers and consisting of Fm1, Fm2, and Fm3, such as the tensor fasciae latae, only one MHC, designated as fast type IIb, could be resolved. In soleus muscle, comprised of both slow-twitch oxidative and fast-twitch oxidative-glycolytic fibers and expressing Sm and Im, two MHC bands were resolved and designated as slow/cardiac beta-MHC and fast type IIa MHC. In muscles expressing a mixture of all three fiber types and a full complement of isomyosins, as seen in the plantaris, the MHC could be resolved into three bands. Light chain profiles were characterized for each muscle type, as well as for the purified isomyosins. These data suggest that Im (IIa) consists of a mixture of fast and slow light chains, whereas Fm (IIb) and Sm (beta) isoforms consist solely of fast- and slow-type light chains, respectively. Polypeptide mapping of denatured myosin extracted from muscles expressing contrasting isoform phenotypes suggests differences in the MHC primary structure between slow, intermediate, and fast myosin isotypes. These findings demonstrate that 1) Fm, Im, and Sm isoforms are differentiated on the bases of both their heavy and light chain components and 2) each isomyosin is distributed in a characteristic fashion among rat hindlimb skeletal muscles. Furthermore, these data suggest that the ratio of isomyosins in a given muscle or muscle region is of physiological importance to the function of that muscle during muscular activity.


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