Acute Exercise Increases Plasma Levels of Muscle-Derived Microvesicles Carrying Fatty Acid Transport Proteins

Abstract Context Microvesicles (MVs) are a class of membrane particles shed by any cell in the body in physiological and pathological conditions. They are considered to be key players in intercellular communication, and with a molecular content reflecting the composition of the cell of origin, they have recently emerged as a promising source of biomarkers in a number of diseases. Objective The effects of acute exercise on the plasma concentration of skeletal muscle-derived MVs (SkMVs) carrying metabolically important membrane proteins were examined. Participants Thirteen men with obesity and type 2 diabetes mellitus (T2DM) and 14 healthy male controls with obesity exercised on a cycle ergometer for 60 minutes. Interventions Muscle biopsies and blood samples—obtained before exercise, immediately after exercise, and 3 hours into recovery—were collected for the analysis of long-chain fatty acid (LCFA) transport proteins CD36 (a scavenger receptor class B protein) and fatty acid transport protein 4 (FATP4) mRNA content in muscle and for flow cytometric studies on circulating SkMVs carrying either LCFA transport protein. Results Besides establishing a flow cytometric approach for the detection of circulating SkMVs and subpopulations carrying either CD36 or FATP4 and thereby adding proof to their existence, we demonstrated an overall exercise-induced change of SkMVs carrying these LCFA transport proteins. A positive correlation between exercise-induced changes in skeletal muscle CD36 mRNA expression and concentrations of SkMVs carrying CD36 was found in T2DM only. Conclusions This approach could add important real-time information about the abundance of LCFA transport proteins present on activated muscle cells in subjects with impaired glucose metabolism.

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Exercise training increases sarcolemmal and mitochondrial fatty acid transport proteins in human skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00073.2010 ◽

2010 ◽

Vol 299 (2) ◽

pp. E180-E188 ◽

Cited By ~ 74

Author(s):

Jason L. Talanian ◽

Graham P. Holloway ◽

Laelie A. Snook ◽

George J. F. Heigenhauser ◽

Arend Bonen ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Human Skeletal Muscle ◽

Transport Proteins ◽

Transport Protein ◽

Fatty Acid Transport ◽

Acid Transport ◽

Fatty Acid Transport Protein ◽

Fatty Acid Transport Proteins ◽

Whole Muscle

Fatty acid oxidation is highly regulated in skeletal muscle and involves several sites of regulation, including the transport of fatty acids across both the plasma and mitochondrial membranes. Transport across these membranes is recognized to be primarily protein mediated, limited by the abundance of fatty acid transport proteins on the respective membranes. In recent years, evidence has shown that fatty acid transport proteins move in response to acute and chronic perturbations; however, in human skeletal muscle the localization of fatty acid transport proteins in response to training has not been examined. Therefore, we determined whether high-intensity interval training (HIIT) increased total skeletal muscle, sarcolemmal, and mitochondrial membrane fatty acid transport protein contents. Ten untrained females (22 ± 1 yr, 65 ± 2 kg; V̇o2peak: 2.8 ± 0.1 l/min) completed 6 wk of HIIT, and biopsies from the vastus lateralis muscle were taken before training, and following 2 and 6 wk of HIIT. Training significantly increased maximal oxygen uptake at 2 and 6 wk (3.1 ± 0.1, 3.3 ± 0.1 l/min). Training for 6 wk increased FAT/CD36 at the whole muscle (10%) and mitochondrial levels (51%) without alterations in sarcolemmal content. Whole muscle plasma membrane fatty acid binding protein (FABPpm) also increased (48%) after 6 wk of training, but in contrast to FAT/CD36, sarcolemmal FABPpm increased (23%), whereas mitochondrial FABPpm was unaltered. The changes on sarcolemmal and mitochondrial membranes occurred rapidly, since differences (≤2 wk) were not observed between 2 and 6 wk. This is the first study to demonstrate that exercise training increases fatty acid transport protein content in whole muscle (FAT/CD36 and FABPpm) and sarcolemmal (FABPpm) and mitochondrial (FAT/CD36) membranes in human skeletal muscle of females. These results suggest that increases in skeletal muscle fatty acid oxidation following training are related in part to changes in fatty acid transport protein content and localization.

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Fatty Acid Transport Protein 1 (FATP1) Localizes in Mitochondria in Mouse Skeletal Muscle and Regulates Lipid and Ketone Body Disposal

PLoS ONE ◽

10.1371/journal.pone.0098109 ◽

2014 ◽

Vol 9 (5) ◽

pp. e98109 ◽

Cited By ~ 12

Author(s):

Maria Guitart ◽

Óscar Osorio-Conles ◽

Thais Pentinat ◽

Judith Cebrià ◽

Judit García-Villoria ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Ketone Body ◽

Transport Protein ◽

Fatty Acid Transport ◽

Acid Transport ◽

Fatty Acid Transport Protein ◽

Mouse Skeletal Muscle

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Insulin and contraction-induced movement of fatty acid transport proteins to skeletal muscle transverse-tubules is distinctly different than to the sarcolemma

Metabolism ◽

10.1016/j.metabol.2012.04.002 ◽

2012 ◽

Vol 61 (11) ◽

pp. 1518-1522 ◽

Cited By ~ 11

Author(s):

Leslie E. Stefanyk ◽

Arend Bonen ◽

David J. Dyck

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Transport Proteins ◽

Fatty Acid Transport ◽

Acid Transport ◽

Transverse Tubules ◽

Fatty Acid Transport Proteins

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Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle

Journal of Clinical Investigation ◽

10.1172/jci200418917 ◽

2004 ◽

Vol 113 (5) ◽

pp. 756-763 ◽

Cited By ~ 176

Author(s):

Jason K. Kim ◽

Ruth E. Gimeno ◽

Takamasa Higashimori ◽

Hyo-Jeong Kim ◽

Hyejeong Choi ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fatty Acid ◽

Transport Protein ◽

Fatty Acid Transport ◽

Acid Transport ◽

Fatty Acid Transport Protein

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Acute endurance exercise increases plasma membrane fatty acid transport proteins in rat and human skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00254.2011 ◽

2012 ◽

Vol 302 (2) ◽

pp. E183-E189 ◽

Cited By ~ 19

Author(s):

Nicolette S. Bradley ◽

Laelie A. Snook ◽

Swati S. Jain ◽

George J. F. Heigenhauser ◽

Arend Bonen ◽

...

Keyword(s):

Skeletal Muscle ◽

Plasma Membrane ◽

Fatty Acid ◽

Human Skeletal Muscle ◽

Transport Proteins ◽

Fatty Acid Transport ◽

Acid Transport ◽

Rat Skeletal Muscle ◽

Muscle Plasma Membrane ◽

Fatty Acid Transport Proteins

Fatty acid transport proteins are present on the plasma membrane and are involved in the uptake of long-chain fatty acids into skeletal muscle. The present study determined whether acute endurance exercise increased the plasma membrane content of fatty acid transport proteins in rat and human skeletal muscle and whether the increase was accompanied by an increase in long-chain fatty acid transport in rat skeletal muscle. Sixteen subjects cycled for 120 min at ∼60 ± 2% V̇o2 peak. Two skeletal muscle biopsies were taken at rest and again following cycling. In a parallel study, eight Sprague-Dawley rats ran for 120 min at 20 m/min, whereas eight rats acted as nonrunning controls. Giant sarcolemmal vesicles were prepared, and protein content of FAT/CD36 and FABPpm was measured in human and rat vesicles and whole muscle homogenate. Palmitate uptake was measured in the rat vesicles. In human muscle, plasma membrane FAT/CD36 and FABPpm protein contents increased 75 and 20%, respectively, following 120 min of exercise. In rat muscle, plasma membrane FAT/CD36 and FABPpm increased 20 and 30%, respectively, and correlated with a 30% increase in palmitate transport following 120 min of running. These data suggest that the translocation of FAT/CD36 and FABPpm to the plasma membrane in rat skeletal muscle is related to the increase in fatty acid transport and oxidation that occurs with endurance running. This study is also the first to demonstrate that endurance cycling induces an increase in plasma membrane FAT/CD36 and FABPpm content in human skeletal muscle, which is predicted to increase fatty acid transport.

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AMPKα is essential for acute exercise-induced gene responses but not for exercise training-induced adaptations in mouse skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00157.2015 ◽

2015 ◽

Vol 309 (11) ◽

pp. E900-E914 ◽

Cited By ~ 20

Author(s):

Joachim Fentz ◽

Rasmus Kjøbsted ◽

Caroline Maag Kristensen ◽

Janne Rasmus Hingst ◽

Jesper Bratz Birk ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Cytochrome C ◽

Exercise Training ◽

Protein Content ◽

Acute Exercise ◽

Fatty Acid Transport ◽

Dependent Manner ◽

Mrna Content ◽

Exercise Induced

Exercise training increases skeletal muscle expression of metabolic proteins improving the oxidative capacity. Adaptations in skeletal muscle by pharmacologically induced activation of 5′-AMP-activated protein kinase (AMPK) are dependent on the AMPKα2 subunit. We hypothesized that exercise training-induced increases in exercise capacity and expression of metabolic proteins, as well as acute exercise-induced gene regulation, would be compromised in muscle-specific AMPKα1 and -α2 double-knockout (mdKO) mice. An acute bout of exercise increased skeletal muscle mRNA content of cytochrome c oxidase subunit I, glucose transporter 4, and VEGF in an AMPK-dependent manner, whereas cluster of differentiation 36 and fatty acid transport protein 1 mRNA content increased similarly in AMPKα wild-type (WT) and mdKO mice. During 4 wk of voluntary running wheel exercise training, the AMPKα mdKO mice ran less than WT. Maximal running speed was lower in AMPKα mdKO than in WT mice but increased similarly in both genotypes with exercise training. Exercise training increased quadriceps protein content of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1), cytochrome c, hexokinase II, plasma membrane fatty acid-binding protein, and citrate synthase activity more in AMPKα WT than in mdKO muscle. However, analysis of a subgroup of mice matched for running distance revealed that only UQCRC1 protein content increased more in WT than in mdKO mice with exercise training. Thus, AMPKα1 and -α2 subunits are important for acute exercise-induced mRNA responses of some genes and may be involved in regulating basal metabolic protein expression but seem to be less important in exercise training-induced adaptations in metabolic proteins.

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