Associations of Serum Adiponectin with Skeletal Muscle Morphology and Insulin Sensitivity

Abstract Context: Skeletal muscle morphology and function are strongly associated with insulin sensitivity. Objective: The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity. Design, Settings, and Participants: This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study. Main Outcome Measures: Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies. Results: In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (β, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (β, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (β, −0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (β difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (β difference, −0.053; 95% confidence interval −0.107, −0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models. Conclusions: Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.

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Lower capillarization, VEGF protein, and VEGF mRNA response to acute exercise in the vastus lateralis muscle of aged vs. young women

Journal of Applied Physiology ◽

10.1152/japplphysiol.00498.2005 ◽

2005 ◽

Vol 99 (5) ◽

pp. 1872-1879 ◽

Cited By ~ 57

Author(s):

Andrea N. Croley ◽

Kevin A. Zwetsloot ◽

Lenna M. Westerkamp ◽

Nicholas A. Ryan ◽

Angela M. Pendergast ◽

...

Keyword(s):

Skeletal Muscle ◽

Vastus Lateralis ◽

Muscle Fibers ◽

Receptor Expression ◽

Vastus Lateralis Muscle ◽

Vegf Receptor ◽

Type I ◽

Type Ii ◽

Vegf Mrna ◽

Vegf Protein

In humans, the majority of studies demonstrate an age-associated reduction in the number of capillaries surrounding skeletal muscle fibers; however, recent reports in rats suggest that muscle capillarization is well maintained with advanced age. In sedentary and trained men, aging lowers the number of capillaries surrounding type II, but not type I, skeletal muscle fibers. The fiber type-specific effect of aging on muscle capillarization is unknown in women. Vascular endothelial growth factor (VEGF) is important in the basal maintenance of skeletal muscle capillarization, and lower VEGF expression is associated with increased age in nonskeletal muscle tissue of women. Compared with young women (YW), we hypothesized that aged women (AW) would demonstrate 1) lower muscle capillarization in a fiber type-specific manner and 2) lower VEGF and VEGF receptor expression at rest and in response to acute exercise. Nine sedentary AW (70 + 8 yr) and 11 YW (22 + 3 yr) had vastus lateralis muscle biopsies obtained before and at 4 h after a submaximal exercise bout for the measurement of morphometry and VEGF and VEGF receptor expression. In AW compared with YW, muscle capillary contacts were lower overall (YW: 2.36 + 0.32 capillaries; AW: 2.08 + 0.17 capillaries), specifically in type II (YW: 2.37 + 0.39 capillaries; AW: 1.91 + 0.36 capillaries) but not type I fibers (YW: 2.36 + 0.34 capillaries; AW: 2.26 + 0.24 capillaries). Muscle VEGF protein was 35% lower at rest, and the exercise-induced increase in VEGF mRNA was 50% lower in AW compared with YW. There was no effect of age on VEGF receptor expression. These results provide evidence that, in the vastus lateralis of women, 1) capillarization surrounding type II muscle fibers is lower in AW compared with YW and 2) resting VEGF protein and the VEGF mRNA response to exercise are lower in AW compared with YW.

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Carbonic anhydrase III in skeletal muscle fibers: an immunocytochemical and biochemical study.

Journal of Histochemistry & Cytochemistry ◽

10.1177/36.7.3133407 ◽

1988 ◽

Vol 36 (7) ◽

pp. 775-782 ◽

Cited By ~ 28

Author(s):

P Frémont ◽

P M Charest ◽

C Côté ◽

P A Rogers

Keyword(s):

Skeletal Muscle ◽

Carbonic Anhydrase ◽

Vastus Lateralis ◽

Muscle Fibers ◽

Water Soluble ◽

Type I ◽

Fiber Types ◽

Thin Sections ◽

Carbonic Anhydrase Iii ◽

Skeletal Muscle Fibers

The objectives of the present study were to determine if carbonic anhydrase III (CA III) demonstrated a specific association for any particular organelle or structure of the skeletal muscle cell and to quantify the activity and content of this enzyme in different types of skeletal muscle fibers. Ultrastructural localization of CA III in the soleus (SOL), deep vastus lateralis (DVL), and superficial vastus lateralis (SVL), composed of predominantly type I, IIa, and IIb fibers, respectively, was performed using a high-resolution immunocytochemical technique and antibody specific for CA III on ultra-thin sections of skeletal muscle embedded in the water-soluble medium polyvinyl alcohol (PVA). The results indicated a uniform distribution of CA III within the sarcomere. Mitochondria, nuclei, triads, Z-, and M-bands were not specifically labeled. Immunoblotting of washed myofibril preparations did not show any detectable CA III associated with this structure. In addition to quantification of the immunogold labeling, CA III activity and content were assayed in the post-mitochondrial supernatant of the three muscles. In the SOL, these values were found to be 3.6-7.6 times higher than in the DVL. The SVL showed a labeling intensity slightly higher than background level, while the enzyme activity and content were indistinguishable from background levels. We therefore conclude that CA III is randomly distributed in the cytoplasm of the three muscle fiber types and that the relative CA III content and activity in the three muscles studied is SOL greater than DVL greater than SVL approximately equal to 0.

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Skeletal muscle phosphatidylcholine and phosphatidylethanolamine are related to insulin sensitivity and respond to acute exercise in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00664.2015 ◽

2016 ◽

Vol 120 (11) ◽

pp. 1355-1363 ◽

Cited By ~ 26

Author(s):

Sean A. Newsom ◽

Joseph T. Brozinick ◽

Katja Kiseljak-Vassiliades ◽

Allison N. Strauss ◽

Samantha D. Bacon ◽

...

Keyword(s):

Mass Spectrometry ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

Acute Exercise ◽

Contractile Function ◽

Vastus Lateralis ◽

Mass Spectrometry Analysis ◽

Vastus Lateralis Muscle ◽

Intravenous Glucose ◽

Exercise In Humans

Several recent reports indicate that the balance of skeletal muscle phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is a key determinant of muscle contractile function and metabolism. The purpose of this study was to determine relationships between skeletal muscle PC, PE and insulin sensitivity, and whether PC and PE are dynamically regulated in response to acute exercise in humans. Insulin sensitivity was measured via intravenous glucose tolerance in sedentary obese adults (OB; n = 14), individuals with type 2 diabetes (T2D; n = 15), and endurance-trained athletes (ATH; n = 15). Vastus lateralis muscle biopsies were obtained at rest, immediately after 90 min of cycle ergometry at 50% maximal oxygen consumption (V̇o2 max), and 2-h postexercise (recovery). Skeletal muscle PC and PE were measured via infusion-based mass spectrometry/mass spectrometry analysis. ATH had greater levels of muscle PC and PE compared with OB and T2D ( P < 0.05), with total PC and PE positively relating to insulin sensitivity (both P < 0.05). Skeletal muscle PC:PE ratio was elevated in T2D compared with OB and ATH ( P < 0.05), tended to be elevated in OB vs. ATH ( P = 0.07), and was inversely related to insulin sensitivity among the entire cohort ( r = −0.43, P = 0.01). Muscle PC and PE were altered by exercise, particularly after 2 h of recovery, in a highly group-specific manner. However, muscle PC:PE ratio remained unchanged in all groups. In summary, total muscle PC and PE are positively related to insulin sensitivity while PC:PE ratio is inversely related to insulin sensitivity in humans. A single session of exercise significantly alters skeletal muscle PC and PE levels, but not PC:PE ratio.

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Changes Induced by Physical Activity and Weight Loss in the Morphology of Intermyofibrillar Mitochondria in Obese Men and Women

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0002 ◽

2006 ◽

Vol 91 (8) ◽

pp. 3224-3227 ◽

Cited By ~ 77

Author(s):

Frederico G. S. Toledo ◽

Simon Watkins ◽

David E. Kelley

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Weight Loss ◽

Insulin Sensitivity ◽

Lifestyle Modification ◽

Vastus Lateralis ◽

Vastus Lateralis Muscle ◽

Mitochondrial Content ◽

The Mean

Abstract Context: In obesity, skeletal muscle insulin resistance may be associated with smaller mitochondria. Objective: Our objective was to examine the effect of a lifestyle-modification intervention on the content and morphology of skeletal muscle mitochondria and its relationship to insulin sensitivity in obese, insulin-resistant subjects. Design: In this prospective interventional study, intermyofibrillar mitochondrial content and size were quantified by transmission electron microscopy with quantitative morphometric analysis of biopsy samples from vastus lateralis muscle. Systemic insulin sensitivity was measured with euglycemic hyperinsulinemic clamps. Setting: The study took place at a university-based clinical research center. Participants: Eleven sedentary, overweight/obese volunteers without diabetes participated in the study. Intervention: Intervention included 16 wk of aerobic training with dietary restriction of 500-1000 kcal/d. Main Outcome Measures: We assessed changes in mitochondrial content and size and changes in insulin sensitivity. Results: The percentage of myofiber volume occupied by mitochondria significantly increased from 3.70 ± 0.31 to 4.87 ± 0.33% after intervention (P = 0.01). The mean individual increase was 42.5 ± 18.1%. There was also a change in the mean cross-sectional mitochondrial area, increasing from a baseline of 0.078 ± 0.007 to 0.091 ± 0.007 μm2 (P < 0.01), a mean increase of 19.2 ± 6.1% per subject. These changes in mitochondrial size and content highly correlated with improvements in insulin resistance (r = 0.68 and 0.72, respectively; P = 0.01). Conclusions: A combined intervention of weight loss and physical activity in previously sedentary obese adults is associated with enlargement of mitochondria and an increase in the mitochondrial content in skeletal muscle. These findings indicate that in obesity with insulin resistance, ultrastructural mitochondrial plasticity is substantially retained and, importantly, that changes in the morphology of mitochondria are associated with improvements in insulin resistance.

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Calcium and strontium contractile activation properties of single skinned skeletal muscle fibres from elderly women 66-90 years of age

10.1101/2021.11.08.466855 ◽

2021 ◽

Author(s):

Sue M Ronaldson ◽

George D Stephenson ◽

Stewart I Head

Keyword(s):

Skeletal Muscle ◽

Elderly Women ◽

Vastus Lateralis ◽

Muscle Fibres ◽

Vastus Lateralis Muscle ◽

Type I ◽

Lateralis Muscle ◽

Slow Twitch ◽

Skeletal Muscle Fibres ◽

Muscle Biopsies

The single skinned muscle fibre technique was used to investigate Ca2+- and Sr2+- activation properties of skeletal muscle fibres from elderly women (66-90 years). Muscle biopsies were obtained from the vastus lateralis muscle. Three populations of muscle fibres were identified according to their specific Sr2+- activation properties: slow-twitch (type I) fast-twitch (type II) and hybrid (type I/II) fibres. All three fibre types were sampled from the biopsies of 66 to 72 years old women, but the muscle biopsies of women older than 80 years yielded only slow-twitch (type I) fibres. The proportion of hybrid fibres in the vastus lateralis muscle of women of circa 70 years of age (24%) was several-fold greater than in the same muscle of adults (<10%), suggesting that muscle remodelling occurs around this age. There were no differences between the Ca2+- and Sr2+- activation properties of slow-twitch fibres from the two groups of elderly women, but there were differences compared with muscle fibres from adults with respect to sensitivity to Ca2+, steepness of the activation curves, and characteristics of the fibre-type dependent phenomenon of spontaneous force oscillations (SOMO) occurring at sub-maximal levels of activation. The maximal Ca2+ activated specific force from all the fibres collected from the seven old women use in the present study was significantly lower by 20% than in the same muscle of adults. Taken together these results show there are qualitative and quantitative changes in the activation properties of the contractile apparatus of muscle fibres from the vastus lateralis muscle of women with advancing age, and that these changes need to be considered when explaining observed changes in womens mobility with aging.

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Do skeletal muscle phenotypic characteristics of Xhosa and Caucasian endurance runners differ when matched for training and racing distances?

Journal of Applied Physiology ◽

10.1152/japplphysiol.01221.2006 ◽

2007 ◽

Vol 103 (3) ◽

pp. 932-940 ◽

Cited By ~ 27

Author(s):

Tertius A. Kohn ◽

Birgitta Essén-Gustavsson ◽

Kathryn H. Myburgh

Keyword(s):

Skeletal Muscle ◽

Fiber Type ◽

Vastus Lateralis ◽

Dry Weight ◽

Vastus Lateralis Muscle ◽

Type I ◽

Endurance Running ◽

Exercise Tests ◽

Black And White ◽

Endurance Runners

Although East African black athletes dominate endurance running events, it is unknown whether black and white endurance runners with similar racing ability, matched for training, may differ in their skeletal muscle biochemical phenotype. Thirteen Xhosa (XR) and 13 Caucasian (CR) endurance runners were recruited and matched for 10-km performance, average preferred racing distance (PRDA), and training volume. Submaximal and maximal exercise tests were done, and vastus lateralis muscle biopsies were taken. XR were significantly lighter and shorter than CR athletes but had similar maximum oxygen consumption corrected for body weight and peak treadmill speed (PTS). XR had lower plasma lactate concentrations at 80% PTS ( P < 0.05) compared with CR. Also, XR had more type IIA (42.4 ± 9.2 vs. 31.3 ± 11.5%, P < 0.05) and less type I fibers (47.8 ± 10.9 vs. 63.1 ± 13.2%, P < 0.05), although oxidative enzyme activities did not differ. Furthermore, XR compared with CR had higher lactate dehydrogenase (LDH) activity in homogenate muscle samples (383 ± 99 vs. 229 ± 85 μmol·min−1·g dry weight−1, P < 0.05) and in both type IIa ( P < 0.05) and type I ( P = 0.05) single-fiber pools. A marked difference ( P < 0.05) in the composition of LDH isoform content was found between the two groups with XR having higher levels of LDH5-4 isoforms (skeletal muscle isozymes; LDH-M) than CR, which was not accounted for by fiber-type differences alone. These results confirm differences in muscle phenotype and physiological characteristics, particularly associated with high-intensity running.

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Activation of the erythropoietin receptor in human skeletal muscle

Acta Endocrinologica ◽

10.1530/eje-09-0342 ◽

2009 ◽

Vol 161 (3) ◽

pp. 427-434 ◽

Cited By ~ 34

Author(s):

Helene Rundqvist ◽

Eric Rullman ◽

Carl Johan Sundberg ◽

Helene Fischer ◽

Katarina Eisleitner ◽

...

Keyword(s):

Skeletal Muscle ◽

Satellite Cells ◽

Human Skeletal Muscle ◽

Acute Exercise ◽

Vastus Lateralis ◽

Muscle Fibers ◽

Receptor Activation ◽

Erythropoietin Receptor ◽

Muscle Performance ◽

Vastus Lateralis Muscle

Objective:Erythropoietin receptor (EPOR) expression in non-hematological tissues has been shown to be activated by locally produced and/or systemically delivered EPO. Improved oxygen homeostasis, a well-established consequence of EPOR activation, is very important for human skeletal muscle performance. In the present study we investigate whether human skeletal muscle fibers and satellite cells express EPOR and if it is activated by exercise.Design and methodsTen healthy males performed 65 min of cycle exercise. Biopsies were obtained from the vastus lateralis muscle and femoral arterio-venous differences in EPO concentrations were estimated.ResultsThe EPOR protein was localized in areas corresponding to the sarcolemma and capillaries. Laser dissection identified EPOR mRNA expression in muscle fibers. Also, EPOR mRNA and protein were both detected in human skeletal muscle satellite cells. In the initial part of the exercise bout there was a release of EPO from the exercising leg to the circulation, possibly corresponding to an increased bioavailability of EPO. After exercise, EPOR mRNA and EPOR-associated JAK2 phosphorylation were increased.ConclusionsInteraction with JAK2 is required for EPOR signaling and the increase found in phosphorylation is therefore closely linked to the activation of EPOR. The receptor activation by acute exercise suggests that signaling through EPOR is involved in exercise-induced skeletal muscle adaptation, thus extending the biological role of EPO into the skeletal muscle.

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Myoglobin levels in individual human skeletal muscle fibers of different types.

Journal of Histochemistry & Cytochemistry ◽

10.1177/32.11.6491255 ◽

1984 ◽

Vol 32 (11) ◽

pp. 1211-1216 ◽

Cited By ~ 48

Author(s):

P M Nemeth ◽

O H Lowry

Keyword(s):

Lactate Dehydrogenase ◽

Citrate Synthase ◽

Vastus Lateralis ◽

Muscle Fibers ◽

Human Muscle ◽

Oxidative Enzymes ◽

Vastus Lateralis Muscle ◽

Type I ◽

Trained Athlete ◽

Fiber Types

An attempt was made to determine the relationship of myoglobin content to specific fiber types in human muscle. Biopsies were obtained from biceps brachii, vastus lateralis, and gastrocnemius muscles of untrained subjects and from the vastus lateralis muscle of a highly trained athlete at peak training and at intervals of no training (detraining). Individual muscle fibers were assayed, by quantitative microanalytical methods, for myoglobin, lactate dehydrogenase, malate dehydrogenase, citrate synthase, beta-hydroxyacyl-coenzyme A dehydrogenase, and adenylokinase activities all on the same fiber. The enzyme levels were used to classify the fibers into type I or II. The results show that the content of myoglobin in human muscle does not differ greatly between fiber types in contrast to other species. The type II fibers contained, on the average, at least two-thirds as much myoglobin as type I fibers. The concentration of myoglobin did not change in either fiber type during detraining (84 days), despite marked changes in lactate dehydrogenase, adenylokinase and the three oxidative enzymes.

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High Incomplete Skeletal Muscle Fatty Acid Oxidation Explains Low Muscle Insulin Sensitivity in Poorly Controlled T2D

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-01727 ◽

2017 ◽

Vol 103 (3) ◽

pp. 882-889 ◽

Cited By ~ 6

Author(s):

Timothy P Gavin ◽

Jacob M Ernst ◽

Hyo-Bum Kwak ◽

Sarah E Caudill ◽

Melissa A Reed ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Insulin Sensitivity ◽

Fatty Acid Oxidation ◽

Mitochondrial Respiration ◽

Vastus Lateralis ◽

Acid Oxidation ◽

Vastus Lateralis Muscle ◽

Intravenous Glucose ◽

Mitochondrial Respiratory

Abstract Context Almost 50% of type 2 diabetic (T2D) patients are poorly controlled [glycated hemoglobin (HbA1c) ≥ 7%]; however, the mechanisms responsible for progressively worsening glycemic control are poorly understood. Lower skeletal muscle mitochondrial respiratory capacity is associated with low insulin sensitivity and the development of T2D. Objective We investigated if skeletal muscle insulin sensitivity (SI) was different between well-controlled T2D (WCD) and poorly controlled T2D (PCD) and if the difference was associated with differences resulting from mitochondrial respiratory function. Design Vastus lateralis muscle mitochondrial respiration, mitochondrial content, mitochondrial enzyme activity, and fatty acid oxidation (FAO) were measured. SI and the acute response to glucose (AIRg) were calculated by MINMOD analysis from glucose and insulin obtained during a modified, frequently sampled, intravenous glucose tolerance test. Results SI and AIRg were lower in PCD than WCD. Muscle incomplete FAO was greater in PCD than WCD and greater incomplete FAO was associated with lower SI and higher HbA1c. Hydroxyacyl-coenzyme A dehydrogenase expression and activity were greater in PCD than WCD. There was no difference in maximal mitochondrial respiration or content between WCD and PCD. Conclusion The current results suggest that greater skeletal muscle incomplete FAO in poorly controlled T2D is due to elevated β oxidation and is associated with worsening muscle SI.

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Cytoskeletal structure of skeletal muscle: identification of an intricate exosarcomeric microtubule lattice in slow- and fast-twitch muscle fibers.

Journal of Histochemistry & Cytochemistry ◽

10.1177/41.7.8515044 ◽

1993 ◽

Vol 41 (7) ◽

pp. 1013-1021 ◽

Cited By ~ 25

Author(s):

S Boudriau ◽

M Vincent ◽

C H Côté ◽

P A Rogers

Keyword(s):

Skeletal Muscle ◽

Muscle Fiber ◽

Vastus Lateralis ◽

Muscle Fiber Types ◽

Vastus Lateralis Muscle ◽

Type I ◽

Fiber Types ◽

Mammalian Skeletal Muscle ◽

Microtubule Network ◽

Fast Twitch

We used immunochemical quantification and indirect immunofluorescence to investigate the cell content, distribution, and organization of microtubules in adult rat slow-twitch soleus and fast-twitch vastus lateralis muscles. An immunoblotting assay demonstrated that the soleus muscle (primarily Type I fibers) was found to have a 1.7-fold higher relative content of alpha-tubulin compared with the superficial portion of the vastus lateralis muscle (primarily Type IIb fibers). Both physiological muscle types revealed a complex arrangement of microtubules which displayed oblique, longitudinal, and transverse orientations within the sarcoplasmic space. The predominance of any one particular orientation varied significantly from one muscle tissue section to another. Nuclei were completely surrounded by a dense net-like structure of microtubules. Both muscle fiber types were found to possess a higher density of microtubules in the subsarcolemmal region. These microtubules followed the contour of the sarcolemma in slightly contracted fibers and showed a fine punctate appearance indicative of a restricted distribution. The immunofluorescence results indicate that microtubules are associated with the sarcolemma and therefore may form a part of the membrane cytoskeletal domain of the muscle fiber. We conclude that the microtubule network of the adult mammalian skeletal muscle fiber constitutes a bone fide component of the exosarcomeric cytoskeletal lattice domain along with the intermediate filaments, and as such could therefore participate in the mechanical integration of the various organelles of the myofibers during the contraction-relaxation cycle.

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