Muscle fiber type I influences lipid oxidation during low-intensity exercise in moderately active middle-aged men

Increasing evidence suggests that TRB3, a mammalian homolog of Drosophila tribbles, plays an important role in cell growth, differentiation, and metabolism. In the liver, TRB3 binds and inhibits Akt activity, whereas in adipocytes, TRB3 upregulates fatty acid oxidation. In cultured muscle cells, TRB3 has been identified as a potential regulator of insulin signaling. However, little is known about the function and regulation of TRB3 in skeletal muscle in vivo. In the current study, we found that 4 wk of voluntary wheel running (6.6 ± 0.4 km/day) increased TRB3 mRNA by 1.6-fold and protein by 2.5-fold in the triceps muscle. Consistent with this finding, muscle-specific transgenic mice that overexpress TRB3 (TG) had a pronounced increase in exercise capacity compared with wild-type (WT) littermates (TG: 1,535 ± 283; WT: 644 ± 67 joules). The increase in exercise capacity in TRB3 TG mice was not associated with changes in glucose uptake or glycogen levels; however, these mice displayed a dramatic shift toward a more oxidative/fatigue-resistant (type I/IIA) muscle fiber type, including threefold more type I fibers in soleus muscles. Skeletal muscle from TRB3 TG mice had significantly decreased PPARα expression, twofold higher levels of miR208b and miR499, and corresponding increases in the myosin heavy chain isoforms Myh7 and Myb7b, which encode these microRNAs. These findings suggest that TRB3 regulates muscle fiber type via a peroxisome proliferator-activated receptor-α (PPAR-α)-regulated miR499/miR208b pathway, revealing a novel function for TRB3 in the regulation of skeletal muscle fiber type and exercise capacity.

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The influence of training status, age, and muscle fiber type on cycling efficiency and endurance performance

Journal of Applied Physiology ◽

10.1152/japplphysiol.00361.2013 ◽

2013 ◽

Vol 115 (5) ◽

pp. 723-729 ◽

Cited By ~ 27

Author(s):

James G. Hopker ◽

Damian A. Coleman ◽

Hannah C. Gregson ◽

Simon A. Jobson ◽

Tobias Von der Haar ◽

...

Keyword(s):

Muscle Fiber ◽

Power Output ◽

Fiber Type ◽

Muscle Fibers ◽

Cycling Performance ◽

Muscle Fiber Type ◽

Type I ◽

Maximal Heart Rate ◽

Training Status ◽

Cycling Efficiency

The purpose of this study was to assess the influence of age, training status, and muscle fiber-type distribution on cycling efficiency. Forty men were recruited into one of four groups: young and old trained cyclists, and young and old untrained individuals. All participants completed an incremental ramp test to measure their peak O2 uptake, maximal heart rate, and maximal minute power output; a submaximal test of cycling gross efficiency (GE) at a series of absolute and relative work rates; and, in trained participants only, a 1-h cycling time trial. Finally, all participants underwent a muscle biopsy of their right vastus lateralis muscle. At relative work rates, a general linear model found significant main effects of age and training status on GE ( P < 0.01). The percentage of type I muscle fibers was higher in the trained groups ( P < 0.01), with no difference between age groups. There was no relationship between fiber type and cycling efficiency at any work rate or cadence combination. Stepwise multiple regression indicated that muscle fiber type did not influence cycling performance ( P > 0.05). Power output in the 1-h performance trial was predicted by average O2 uptake and GE, with standardized β-coefficients of 0.94 and 0.34, respectively, although some mathematical coupling is evident. These data demonstrate that muscle fiber type does not affect cycling efficiency and was not influenced by the aging process. Cycling efficiency and the percentage of type I muscle fibers were influenced by training status, but only GE at 120 revolutions/min was seen to predict cycling performance.

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Muscle fiber type specificity in insulin signal transduction

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.277.6.r1690 ◽

1999 ◽

Vol 277 (6) ◽

pp. R1690-R1696 ◽

Cited By ~ 33

Author(s):

Xiao Mei Song ◽

Jeffrey W. Ryder ◽

Yuichi Kawano ◽

Alexander V. Chibalin ◽

Anna Krook ◽

...

Keyword(s):

Insulin Receptor ◽

Tyrosine Phosphorylation ◽

Muscle Fiber ◽

Fiber Type ◽

Insulin Response ◽

Muscle Fiber Type ◽

Specific Response ◽

Type I ◽

Akt Kinase ◽

Sustained Activity

We determined the muscle fiber type-specific response of intracellular signaling proteins to insulin. Epitrochlearis (Epi; 15% type I, 20% type IIa, and 65% type IIb), soleus (84, 16, and 0%), and extensor digitorum longus (EDL; 3, 57, and 40%) muscles from Wistar rats were incubated without or with 120 nM insulin (3–40 min). Peak insulin receptor (IR) tyrosine phosphorylation was reached after 6 (soleus) and 20 (Epi and EDL) min, with sustained activity throughout insulin exposure (40 min). Insulin increased insulin receptor substrate (IRS)-1 and IRS-2 tyrosine phosphorylation and phosphotyrosine-associated phosphatidylinositol (PI)-3-kinase activity to a maximal level after 3–10 min, with subsequent downregulation. Akt kinase phosphorylation peaked at 20 min, with sustained activity throughout insulin exposure. Importantly, the greatest insulin response for all signaling intermediates was observed in soleus, whereas the insulin response between EDL and Epi was similar. Protein expression of the p85α-subunit of PI 3-kinase and Akt kinase, but not IR, IRS-1, or IRS-2, was greater in oxidative versus glycolytic muscle. In conclusion, increased function and/or expression of key proteins in the insulin-signaling cascade contribute to fiber type-specific differences in insulin action in skeletal muscle.

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Interrelationships between muscle morphology, insulin action, and adiposity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.270.6.r1332 ◽

1996 ◽

Vol 270 (6) ◽

pp. R1332-R1339 ◽

Cited By ~ 23

Author(s):

A. D. Kriketos ◽

D. A. Pan ◽

S. Lillioja ◽

G. J. Cooney ◽

L. A. Baur ◽

...

Keyword(s):

Insulin Resistance ◽

Body Fat ◽

Muscle Fiber ◽

Insulin Action ◽

Fiber Type ◽

Oxidative Capacity ◽

Muscle Fiber Type ◽

Type I ◽

Fa Composition ◽

Type I Fibers

There is evidence that insulin resistance and obesity are associated with relative increases in the proportion of glycolytic type IIb muscle fibers and decreases in the proportion of oxidative type I fibers. Futhermore, insulin resistance and obesity are associated with the fatty acid (FA) profile of structural membrane lipids. The present study was undertaken to define interrelationships between muscle fiber type and oxidative capacity, muscle membrane FA composition, and insulin action and obesity. Muscle morphology, insulin action, and body fat content were measured in 48 male nondiabetic Pima Indians. Percent body fat (pFAT, determined by hydrodensitometry) correlated negatively with percentage of type I fibers (r = -0.44, P = 0.002) and positively with percentage of type IIb fibers (r = 0.40, P = 0.005). Consistent with this finding, pFAT was also significantly related to oxidative capacity of muscle, as assessed by NADH staining (r = -0.47, P = 0.0007) and citrate synthase (CS) activity (r = -0.43, P = 0.008). Insulin action was correlated with oxidative capacity (CS; r = 0.41, P = 0.01) and weakly correlated with percentage of type IIb fibers (r = -0.29, P = 0.05). In addition, relationships were shown between muscle fiber type and FA composition (e.g., percentage of type I fibers related to n-3 FA; r = 0.37, P = 0.01). Thus leaness and insulin sensitivity are associated with increased oxidative capacity and unsaturation of membranes in skeletal muscle. Present studies support the hypothesis that muscle oxidative capacity and fiber type may play a genetically determined or an environmentally modified role in development of obesity and insulin resistance.

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Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00103.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. E686-E695 ◽

Cited By ~ 42

Author(s):

Rachel L. G. S. Oliveira ◽

Mirian Ueno ◽

Cláudio T. de Souza ◽

Márcio Pereira-da-Silva ◽

Alessandra L. Gasparetti ◽

...

Keyword(s):

Insulin Receptor ◽

Glucose Uptake ◽

Tyrosine Phosphorylation ◽

Muscle Fiber ◽

Cold Exposure ◽

Antisense Oligonucleotide ◽

Fiber Type ◽

Muscle Fiber Type ◽

Membrane Localization ◽

Type I

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) participates in control of expression of genes involved in adaptive thermogenesis, muscle fiber type differentiation, and fuel homeostasis. The objective of the present study was to evaluate the participation of cold-induced PGC-1α expression in muscle fiber type-specific activity of proteins that belong to the insulin-signaling pathway. Rats were exposed to 4°C for 4 days and acutely treated with insulin in the presence or absence of an antisense oligonucleotide to PGC-1α. Cold exposure promoted a significant increase of PGC-1α and uncoupling protein-3 protein expression in type I and type II fibers of gastrocnemius muscle. In addition, cold exposure led to higher glucose uptake during a hyperinsulinemic clamp, which was accompanied by higher expression and membrane localization of GLUT4 in both muscle fiber types. Cold exposure promoted significantly lower insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and Ser473 phosphorylation of acute transforming retrovirus thymoma (Akt) and an insulin-independent increase of Thr172 phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK). Inhibition of PGC-1α expression in cold-exposed rats by antisense oligonucleotide treatment diminished glucose clearance rates during a hyperinsulinemic clamp and reduced expression and membrane localization of GLUT4. Reduction of PGC-1α expression resulted in no modification of insulin-induced tyrosine phosphorylation of the IR and Ser473 phosphorylation of Akt. Finally, reduction of PGC-1α resulted in lower Thr172 phosphorylation of AMPK. Thus cold-induced hyperexpression of PGC-1α participates in control of skeletal muscle glucose uptake through a mechanism that controls GLUT4 expression and subcellular localization independent of the IR and Akt activities but dependent on AMPK.

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Muscle fiber type composition and fiber size in successfully and unsuccessfully endurance-raced horses

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.4.1758 ◽

1993 ◽

Vol 75 (4) ◽

pp. 1758-1766 ◽

Cited By ~ 47

Author(s):

J. L. Rivero ◽

A. L. Serrano ◽

P. Henckel ◽

E. Aguera

Keyword(s):

Muscle Fiber ◽

Fiber Type ◽

Reductase Activity ◽

Muscle Fiber Type ◽

Lower Percentage ◽

Type I ◽

Fiber Type Composition ◽

Type Composition ◽

Fiber Size ◽

Muscle Fiber Type Composition

Triplicate biopsies from three different depths of the gluteus medius muscle were obtained in 36 endurance-raced horses, aged 8.42 +/- 2.85 yr. Twenty of the horses were considered excellent endurance performers according to the mean speed of their three fastest records in endurance events for the past 2 or 3 years, whereas 16 were moderate performers, with a mean racing speed < 12.5 km/h (in 120- to 180-km endurance rides), < 14 km/h (in 80- to 120-km endurance rides), or < 13.5 km/h (in 40- to 60-km endurance rides). Significant differences in muscle fiber type composition and fiber size were recorded; excellent performers had a higher percentage and a larger size of type I and type IIa fibers (high and low myosin adenosinetriphosphatase activity at pH 4.5, respectively) and a lower percentage of type IIb fibers (moderate myosin adenosinetriphosphatase activity at pH 4.5), including both type IIb oxidative (moderate to high NADH-tetrazolium reductase activity) and IIb nonoxidative (low NADH-tetrazolium reductase activity). The differences in distribution of myofiber types and in fiber sizes were more marked in the deeper parts compared with the superficial regions of muscle. Our results also imply a greater homogeneity among the fiber type sizes across the muscle in horses with a superior endurance performance than in horses that had been poorly or moderately endurance raced. Thus the results show that fiber type proportions and fiber size in equine skeletal muscle are directly related to the athletic ability of the horse for endurance events.

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The Single Fiber EMG of Type I and II Muscle Fiber. Classification of Muscle Fiber Type of Hen.

The Japanese Journal of Rehabilitation Medicine ◽

10.2490/jjrm1963.29.833 ◽

1992 ◽

Vol 29 (10) ◽

pp. 833-835

Author(s):

Masayasu MIZUNO

Keyword(s):

Muscle Fiber ◽

Fiber Type ◽

Muscle Fiber Type ◽

Single Fiber ◽

Type I

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Skeletal muscle histochemical and biochemical characteristics in sedentary male and female subjects

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y85-005 ◽

1985 ◽

Vol 63 (1) ◽

pp. 30-35 ◽

Cited By ~ 113

Author(s):

J. A. Simoneau ◽

G. Lortie ◽

M. R. Boulay ◽

M.-C. Thibault ◽

G. Thériault ◽

...

Keyword(s):

Muscle Fiber ◽

Enzyme Activities ◽

Fiber Type ◽

Muscle Fiber Type ◽

Vastus Lateralis Muscle ◽

Type I ◽

Male And Female ◽

Type Distribution ◽

Fiber Type Distribution ◽

Female Subjects

The purpose of this study was to assess the relationship between muscle fiber type distribution and enzymatic characteristics in sedentary male and female subjects. Muscle biopsy samples from the vastus lateralis muscle of 38 females and 37 males were analyzed to determine the fiber type composition (I, IIa, and IIb), the fiber size, and maximal activities of enzyme markers of energy metabolic pathways. Significant correlations were found (p < 0.05) between percent fiber type I area and hexokinase (r = −0.39), phosphofructokinase (r = −0.39), lactate dehydrogenase (r = −0.41), and oxoglutarate dehydrogenase (r = 0.33) activities, whereas such correlations with total phosphorylase (r = −0.02), malate dehydrogenase (r = 0.12), and 3-hydroxyacyl CoA dehydrogenase (r = 0.12) activities were not significant. The results of the present study also suggest the presence of a significant but low covariation of less than 30% between the fiber type distribution and muscle enzyme activities. They confirm the presence of an important metabolic heterogeneity independent of the muscle fiber type distribution in sedentary male and female subjects. Moreover, these results indicate that sedentary males exhibit a lower mean value of percent fiber type I and higher glycolytic enzyme activities than sedentary females.

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Fnip1 regulates skeletal muscle fiber type specification, fatigue resistance, and susceptibility to muscular dystrophy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1413021112 ◽

2014 ◽

Vol 112 (2) ◽

pp. 424-429 ◽

Cited By ~ 43

Author(s):

Nicholas L. Reyes ◽

Glen B. Banks ◽

Mark Tsang ◽

Daciana Margineantu ◽

Haiwei Gu ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscular Dystrophy ◽

Muscle Fiber ◽

Skeletal Muscles ◽

Fiber Type ◽

Skeletal Muscle Fiber ◽

Muscle Fiber Type ◽

Type I ◽

Slow Twitch ◽

Type Specification

Mammalian skeletal muscle is broadly characterized by the presence of two distinct categories of muscle fibers called type I “red” slow twitch and type II “white” fast twitch, which display marked differences in contraction strength, metabolic strategies, and susceptibility to fatigue. The relative representation of each fiber type can have major influences on susceptibility to obesity, diabetes, and muscular dystrophies. However, the molecular factors controlling fiber type specification remain incompletely defined. In this study, we describe the control of fiber type specification and susceptibility to metabolic disease by folliculin interacting protein-1 (Fnip1). Using Fnip1 null mice, we found that loss of Fnip1 increased the representation of type I fibers characterized by increased myoglobin, slow twitch markers [myosin heavy chain 7 (MyH7), succinate dehydrogenase, troponin I 1, troponin C1, troponin T1], capillary density, and mitochondria number. Cultured Fnip1-null muscle fibers had higher oxidative capacity, and isolated Fnip1-null skeletal muscles were more resistant to postcontraction fatigue relative to WT skeletal muscles. Biochemical analyses revealed increased activation of the metabolic sensor AMP kinase (AMPK), and increased expression of the AMPK-target and transcriptional coactivator PGC1α in Fnip1 null skeletal muscle. Genetic disruption of PGC1α rescued normal levels of type I fiber markers MyH7 and myoglobin in Fnip1-null mice. Remarkably, loss of Fnip1 profoundly mitigated muscle damage in a murine model of Duchenne muscular dystrophy. These results indicate that Fnip1 controls skeletal muscle fiber type specification and warrant further study to determine whether inhibition of Fnip1 has therapeutic potential in muscular dystrophy diseases.

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