Enhanced Skeletal Muscle Oxidative Capacity and Capillary-to-Fiber Ratio Following Moderately Increased Testosterone Exposure in Young Healthy Women

Background: Recently, it was shown that exogenously administered testosterone enhances endurance capacity in women. In this study, our understanding on the effects of exogenous testosterone on key determinants of oxygen transport and utilization in skeletal muscle is expanded.Methods: In a double-blinded, randomized, placebo-controlled trial, 48 healthy active women were randomized to 10 weeks of daily application of 10 mg of testosterone cream or placebo. Before and after the intervention, VO2 max, body composition, total hemoglobin (Hb) mass and blood volumes were assessed. Biopsies from the vastus lateralis muscle were obtained before and after the intervention to assess mitochondrial protein abundance, capillary density, capillary-to-fiber (C/F) ratio, and skeletal muscle oxidative capacity.Results: Maximal oxygen consumption per muscle mass, Hb mass, blood, plasma and red blood cell volumes, capillary density, and the abundance of mitochondrial protein levels (i.e., citrate synthase, complexes I, II, III, IV-subunit 2, IV-subunit 4, and V) were unchanged by the intervention. However, the C/F ratio, specific mitochondrial respiratory flux activating complex I and linked complex I and II, uncoupled respiration and electron transport system capacity, but not leak respiration or fat respiration, were significantly increased following testosterone administration compared to placebo.Conclusion: This study provides novel insights into physiological actions of increased testosterone exposure on key determinants of oxygen diffusion and utilization in skeletal muscle of women. Our findings show that higher skeletal muscle oxidative capacity coupled to higher C/F ratio could be major contributing factors that improve endurance performance following moderately increased testosterone exposure.

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Temperament influences mitochondrial capacity in skeletal muscle from 8 through 18 mo of age in Brahman heifers

Journal of Animal Science ◽

10.1093/jas/skaa291 ◽

2020 ◽

Vol 98 (10) ◽

Author(s):

Randi N Owen ◽

Christine M Latham ◽

Charles R Long ◽

Ronald D Randel ◽

Thomas H Welsh ◽

...

Keyword(s):

Skeletal Muscle ◽

Product Quality ◽

Repeated Measures ◽

Complex I ◽

Citrate Synthase ◽

Serum Cortisol ◽

System Capacity ◽

Complex Ii ◽

Potential Link ◽

Muscle Groups

Abstract Temperamental cattle tend to yield carcasses of poorer quality, and Brahman cattle are reportedly more temperamental than non-indicus cattle breeds. A potential link between temperament and product quality may be mitochondrial activity. We hypothesized that mitochondrial measures would be greater in temperamental compared with calm heifers and that the relationships between temperament and mitochondria would persist as heifers age. Serum cortisol and skeletal muscle (longissimus thoracis [LT] and trapezius [TRAP]) mitochondrial profiles and antioxidant activities were quantified from the same calm (n = 6) and temperamental (n = 6) Brahman heifers at 8, 12, and 18 mo of age. Data were analyzed using a mixed model ANOVA in SAS (9.4) with repeated measures. Serum cortisol was greater in temperamental compared with calm heifers throughout the study (P = 0.02). Mitochondrial volume density (citrate synthase [CS] activity) increased over time (P < 0.0001) but was similar between temperament and muscle groups. Mitochondrial function (cytochrome c oxidase activity) was greatest in the temperamental LT at 8 mo of age (P ≤ 0.0006), greatest in the temperamental TRAP at 18 mo of age (P ≤ 0.003), and did not differ by temperament at 12 mo of age. Integrative (relative to tissue wet weight) mitochondrial oxidative phosphorylation capacity with complex I substrates (PCI), PCI plus complex II substrate (PCI+II), noncoupled electron transfer system capacity (ECI+II), and E with functional complex II only (ECII) were greater in the TRAP than LT for calm heifers at all ages (P ≤ 0.002), but were similar between muscle groups in temperamental heifers. Overall, calm heifers tended to have greater intrinsic (relative to CS activity) PCI and flux control of PCI+II (P ≤ 0.1) than temperamental heifers, indicating greater utilization of complex I paired with greater coupling efficiency in calm heifers. Within the LT, integrative PCI+II was greater (P = 0.05) and ECI+II tended to be greater (P = 0.06) in temperamental compared with calm heifers. From 8- to 18-mo old, glutathione peroxidase (GPx) activity decreased (P < 0.0001) and superoxide dismutase activity increased (P = 0.02), and both were similar between muscle groups. The activity of GPx was greater in temperamental compared with calm heifers at 8 (P = 0.004) but not at 12 or 18 mo of age. These results detail divergent skeletal muscle mitochondrial characteristics of live Brahman heifers according to temperament, which should be further investigated as a potential link between temperament and product quality.

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Muscle Oxidative Capacity Is a Better Predictor of Insulin Sensitivity than Lipid Status

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2003-030791 ◽

2003 ◽

Vol 88 (11) ◽

pp. 5444-5451 ◽

Cited By ~ 159

Author(s):

Clinton R. Bruce ◽

Mitchell J. Anderson ◽

Andrew L. Carey ◽

David G. Newman ◽

Arend Bonen ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Citrate Synthase ◽

Oxidative Capacity ◽

Fatty Acyl ◽

Whole Body ◽

Before And After ◽

Hydroxyacyl Coa Dehydrogenase ◽

Long Chain

Abstract We determined whole-body insulin sensitivity, long-chain fatty acyl coenzyme A (LCACoA) content, skeletal muscle triglyceride (TGm) concentration, fatty acid transporter protein content, and oxidative enzyme activity in eight patients with type 2 diabetes (TYPE 2); six healthy control subjects matched for age (OLD), body mass index, percentage of body fat, and maximum pulmonary O2 uptake; nine well-trained athletes (TRAINED); and four age-matched controls (YOUNG). Muscle biopsies from the vastus lateralis were taken before and after a 2-h euglycemic-hyperinsulinemic clamp. Oxidative enzyme activities, fatty acid transporters (FAT/CD36 and FABPpm), and TGm were measured from basal muscle samples, and total LCACoA content was determined before and after insulin stimulation. Whole-body insulin-stimulated glucose uptake was lower in TYPE 2 (P < 0.05) than in OLD, YOUNG, and TRAINED. TGm was elevated in TYPE 2 compared with all other groups (P < 0.05). However, both basal and insulin-stimulated skeletal muscle LCACoA content were similar. Basal citrate synthase activity was higher in TRAINED (P < 0.01), whereas β-hydroxyacyl CoA dehydrogenase activity was higher in TRAINED compared with TYPE 2 and OLD. There was a significant relationship between the oxidative capacity of skeletal muscle and insulin sensitivity (citrate synthase, r = 0.71, P < 0.001; β-hydroxyacyl CoA dehydrogenase, r = 0.61, P = 0.001). No differences were found in FAT/CD36 protein content between groups. In contrast, FABPpm protein was lower in OLD compared with TYPE 2 and YOUNG (P < 0.05). In conclusion, despite markedly elevated skeletal muscle TGm in type 2 diabetic patients and strikingly different levels of whole-body glucose disposal, both basal and insulin-stimulated LCACoA content were similar across groups. Furthermore, skeletal muscle oxidative capacity was a better predictor of insulin sensitivity than either TGm concentration or long-chain fatty acyl CoA content.

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Increased oxidative capacity does not protect skeletal muscle fibers from eccentric contraction-induced injury

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.274.5.r1300 ◽

1998 ◽

Vol 274 (5) ◽

pp. R1300-R1308 ◽

Cited By ~ 7

Author(s):

T. J. Patel ◽

D. Cuizon ◽

O. Mathieu-Costello ◽

J. Fridén ◽

R. L. Lieber

Keyword(s):

Electrical Stimulation ◽

Citrate Synthase ◽

Fiber Type ◽

Exercise Bout ◽

Eccentric Contraction ◽

Capillary Density ◽

Oxidative Capacity ◽

Training Effect ◽

Muscle Oxidative Capacity ◽

Tetanic Tension

Isometric electrical stimulation was delivered to rabbit dorsiflexor muscles at 10 Hz for 1 s on and 1 s off over 30 min, 5 days/wk for 3 wk to induce an increase in muscle oxidative capacity. Stimulation-trained muscles as well as untrained muscles were then subjected to a 30-min eccentric exercise bout to test whether increased oxidative capacity provided a protective effect against muscle injury. Electrical stimulation resulted in significant training of both the extensor digitorum longus (EDL) and tibialis anterior (TA) muscles, with EDL citrate synthase (CS) activity increasing an average of 67% ( P < 0.0001) and TA CS activity increasing by 27% ( P < 0.05). For all parameters measured, the magnitude of change was much greater for EDL than for TA muscle. Dorsiflexor fatigability decreased significantly during the 3-wk training period ( P < 0.0001), whereas the EDL and TA individually showed strong decreasing trends in fatigability after training. TA and EDL capillary density measured histomorphometrically increased from 839 ± 56 to 1,026 ± 71 mm−2( P = 0.07) and from 589 ± 37 to 792 ± 66 mm−2( P < 0.05), respectively. TA and EDL capillary-to-fiber ratio increased from 1.32 ± 0.10 to 1.55 ± 0.16 ( P > 0.2) and 1.08 ± 0.07 to 1.36 ± 0.14 ( P > 0.1), respectively. Type 2A fiber type percentage increased after stimulation training by 68% ( P < 0.0001) for the EDL and by 32% ( P > 0.1) for the TA at the expense of type 2D fibers. Despite the large training effect for the EDL and the modest training effect for the TA, no differences were observed between stimulation-trained and untrained groups for maximum dorsiflexion torque ( P > 0.3) or maximum tetanic tension ( P > 0.3) after eccentric contraction-induced injury. Additionally, no significant correlation was observed between CS activity and maximum tetanic tension after eccentric contraction-induced injury for either muscle ( P > 0.2). Thus we conclude that increasing muscle oxidative capacity by isometric electrical stimulation training did not protect muscle against eccentric contraction-induced injury.

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Skeletal muscle of females and males with constitutional thinness: a low intramuscular lipid content and oxidative profile

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2020-0068 ◽

2020 ◽

Vol 45 (11) ◽

pp. 1287-1298 ◽

Cited By ~ 1

Author(s):

Mélina Bailly ◽

Natacha Germain ◽

Léonard Féasson ◽

Frédéric Costes ◽

Bruno Estour ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Control ◽

Glycogen Content ◽

Citrate Synthase ◽

Fiber Type ◽

Muscle Fibers ◽

Oxidative Capacity ◽

Normal Weight ◽

Type I ◽

Before And After

Constitutional thinness (CT) is a nonpathological state of underweight. The current study aimed to explore skeletal muscle energy storage in individuals with CT and to further characterize muscle phenotype at baseline and in response to overfeeding. Thirty subjects with CT (15 females, 15 males) and 31 normal-weight control subjects (16 females, 15 males) participated in the study. Histological and enzymological analyses were performed on muscle biopsy specimens before and after overfeeding. In the skeletal muscle of CT participants compared with controls, we observed a lower content of intramuscular triglycerides for type I (−17%, p < 0.01) and type IIA (−14%, p < 0.05) muscle fibers, a lower glycogen content for type I (−6%, p < 0.01) and type IIA (−5%, p < 0.05) muscle fibers, a specific fiber-type distribution, a marked muscle hypotrophy (−20%, p < 0.001), a low capillary-to-fiber ratio (−19%, p < 0.001), and low citrate synthase activity (−18%, p < 0.05). In response to overfeeding, CT participants increased their intramuscular triglycerides content in type I (+10%, p < 0.01) and type IIA (+9%, p < 0.01) muscle fibers. CT individuals seem to present an unusual muscle phenotype and different adaptations to overfeeding compared with normal-weight individuals, suggesting a specific energy metabolism and muscle adaptations. ClinicalTrials.gov registration no. NCT02004821. Novelty Low intramuscular triglycerides and glycogen content in skeletal muscle of constitutionally thin individuals. Low oxidative capacity, low capillary supply, and fiber hypotrophy in skeletal muscle of constitutionally thin individuals. Increase in intramuscular triglycerides in constitutional thinness in response to overfeeding.

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162 PGC-1alpha correlates with cardiac and skeletal muscle oxidative capacity in heart failure

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(03)90091-9 ◽

2003 ◽

Vol 2 (1) ◽

pp. 29-30

Author(s):

A GARNIER ◽

D FORTIN ◽

C DELOMENIE ◽

I MOMKEN ◽

V VEKSLER ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Oxidative Capacity ◽

Muscle Oxidative Capacity

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Interval and Continuous Exercise Training Produce Similar Increases in Skeletal Muscle and Left Ventricle Microvascular Density in Rats

BioMed Research International ◽

10.1155/2013/752817 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Flávio Pereira ◽

Roger de Moraes ◽

Eduardo Tibiriçá ◽

Antonio C. L. Nóbrega

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Left Ventricle ◽

Body Weight Gain ◽

Interval Training ◽

Capillary Density ◽

Oxidative Capacity ◽

Constant Load ◽

Continuous Exercise ◽

Muscle Ct

Interval training (IT), consisting of alternated periods of high and low intensity exercise, has been proposed as a strategy to induce more marked biological adaptations than continuous exercise training (CT). The purpose of this study was to assess the effects of IT and CT with equivalent total energy expenditure on capillary skeletal and cardiac muscles in rats. Wistar rats ran on a treadmill for 30 min per day with no slope (0%), 4 times/week for 13 weeks. CT has constant load of 70% max; IT has cycles of 90% max for 1 min followed by 1 min at 50% max. CT and IT increased endurance and muscle oxidative capacity and attenuated body weight gain to a similar extent (P>0.05). In addition, CT and IT similarly increased functional capillary density of skeletal muscle (CT:30.6±11.7%; IT:28.7±11.9%) and the capillary-to-fiber ratio in skeletal muscle (CT:28.7±14.4%; IT:40.1±17.2%) and in the left ventricle (CT:57.3±53.1%; IT:54.3±40.5%). In conclusion, at equivalent total work volumes, interval exercise training induced similar functional and structural alterations in the microcirculation of skeletal muscle and myocardium in healthy rats compared to continuous exercise training.

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