Adiponectin—Consideration for its Role in Skeletal Muscle Health

Adiponectin regulates metabolism through blood glucose control and fatty acid oxidation, partly mediated by downstream effects of adiponectin signaling in skeletal muscle. More recently, skeletal muscle has been identified as a source of adiponectin expression, fueling interest in the role of adiponectin as both a circulating adipokine and a locally expressed paracrine/autocrine factor. In addition to being metabolically responsive, skeletal muscle functional capacity, calcium handling, growth and maintenance, regenerative capacity, and susceptibility to chronic inflammation are all strongly influenced by adiponectin stimulation. Furthermore, physical exercise has clear links to adiponectin expression and circulating concentrations in healthy and diseased populations. Greater physical activity is generally related to higher adiponectin expression while lower adiponectin levels are found in inactive obese, pre-diabetic, and diabetic populations. Exercise training typically restores plasma adiponectin and is associated with improved insulin sensitivity. Thus, the role of adiponectin signaling in skeletal muscle has expanded beyond that of a metabolic regulator to include several aspects of skeletal muscle function and maintenance critical to muscle health, many of which are responsive to, and mediated by, physical exercise.

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The role of microRNAs in skeletal muscle health and disease

Frontiers in Bioscience ◽

10.2741/4298 ◽

2015 ◽

Vol 20 (1) ◽

pp. 37-77 ◽

Cited By ~ 34

Author(s):

John J. McCarthy

Keyword(s):

Skeletal Muscle ◽

Health And Disease ◽

Muscle Health

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Dietary Patterns, Skeletal Muscle Health, and Sarcopenia in Older Adults

Nutrients ◽

10.3390/nu11040745 ◽

2019 ◽

Vol 11 (4) ◽

pp. 745 ◽

Cited By ~ 30

Author(s):

Antoneta Granic ◽

Avan Sayer ◽

Sian Robinson

Keyword(s):

Older Adults ◽

Skeletal Muscle ◽

Dietary Patterns ◽

Healthy Eating Index ◽

Muscle Disease ◽

Nutritional Epidemiology ◽

Societal Implications ◽

Increased Risk ◽

Muscle Health

In recent decades, the significance of diet and dietary patterns (DPs) for skeletal muscle health has been gaining attention in ageing and nutritional research. Sarcopenia, a muscle disease characterised by low muscle strength, mass, and function is associated with an increased risk of functional decline, frailty, hospitalization, and death. The prevalence of sarcopenia increases with age and leads to high personal, social, and economic costs. Finding adequate nutritional measures to maintain muscle health, preserve function, and independence for the growing population of older adults would have important scientific and societal implications. Two main approaches have been employed to study the role of diet/DPs as a modifiable lifestyle factor in sarcopenia. An a priori or hypothesis-driven approach examines the adherence to pre-defined dietary indices such as the Mediterranean diet (MED) and Healthy Eating Index (HEI)—measures of diet quality—in relation to muscle health outcomes. A posteriori or data-driven approaches have used statistical tools—dimension reduction methods or clustering—to study DP-muscle health relationships. Both approaches recognise the importance of the whole diet and potential cumulative, synergistic, and antagonistic effects of foods and nutrients on ageing muscle. In this review, we have aimed to (i) summarise nutritional epidemiology evidence from four recent systematic reviews with updates from new primary studies about the role of DPs in muscle health, sarcopenia, and its components; (ii) hypothesise about the potential mechanisms of ‘myoprotective’ diets, with the MED as an example, and (iii) discuss the challenges facing nutritional epidemiology to produce the higher level evidence needed to understand the relationships between whole diets and healthy muscle ageing.

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Genetic downregulation of receptor-interacting protein 140 uncovers the central role of Akt signalling in the regulation of fatty acid oxidation in skeletal muscle cells

Experimental Physiology ◽

10.1113/expphysiol.2012.068833 ◽

2012 ◽

Vol 98 (2) ◽

pp. 514-525 ◽

Cited By ~ 4

Author(s):

Silvana Constantinescu ◽

Lorraine P. Turcotte

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Acid Oxidation ◽

Interacting Protein

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The role of protein-mediated transport in regulating mitochondrial long-chain fatty acid oxidation

Applied Physiology Nutrition and Metabolism ◽

10.1139/h07-172 ◽

2008 ◽

Vol 33 (1) ◽

pp. 141-142

Author(s):

Graham Paul Holloway

Keyword(s):

Skeletal Muscle ◽

Plasma Membrane ◽

Fatty Acid ◽

Muscle Contraction ◽

Fatty Acid Oxidation ◽

Acid Oxidation ◽

Mitochondrial Content ◽

Palmitate Oxidation ◽

Long Chain

This thesis is an investigation of the role of fatty acid translocase (FAT/CD36), plasma membrane associated fatty acid binding protein (FABPpm), and carnitine palmitoyltransferase I (CPTI) in transporting long-chain fatty acids (LCFAs) across mitochondrial membranes. Maximal CPTI activity, as well as the sensitivity of CPTI for its substrate palmitoyl-CoA (P-CoA) and its inhibitor malonyl-CoA (M-CoA), were measured in mitochondria isolated from human vastus lateralis muscles at rest and following muscle contraction. Exercise did not alter maximal CPTI activity or the sensitivity of CPTI for P-CoA. In contrast, exercise progressively attenuated the ability of M-CoA to inhibit CPTI activity. Mitochondrial FAT/CD36 protein content was also measured at rest, during, and following 2 h of cycling at ~60% maximal oxygen uptake. Exercise progressively increased the content of mitochondrial FAT/CD36 (+59%), which was significantly (p < 0.05) correlated with palmitate oxidation during exercise (r = 0.52), while palmitate oxidation was inhibited ~80% by the administration of a specific FAT/CD36 inhibitor. These data suggest that alterations in CPTI M-CoA sensitivity and increases in mitochondrial FAT/CD36 coordinate exercise-induced increases in fatty acid oxidation. FABPpm, another plasma membrane transport protein, has identical amino acid sequence to mitochondrial aspartate aminotransferase (mAspAT). Since FABPpm contributes to plasma membrane fatty acid transport, the role of FABPpm with respect to mitochondrial LCFA transport was investigated. However, unlike FAT/CD36, muscle contraction did not induce an increase in mitochondrial FABPpm protein in rat or human skeletal muscle. In addition, electrotransfecting FABPpm cDNA into rat skeletal muscle upregulated this protein in mitochondria by 80% without altering mitochondrial palmitate oxidation. In contrast, electrotransfection increased mAspAT activity by 90%, and this was correlated (r = 0.75; p < 0.01) with FABPpm protein. These data suggest that FABPpm does not contribute to the regulation of mitochondrial LCFA transport. Previously, it has been suggested that mitochondria from obese individuals contain an inherent dysfunction to oxidize LCFAs. In age-matched lean (BMI = 23.3 ± 0.7 kg·m–2) and obese (BMI = 37.6 ± 2.2 kg·m–2) individuals, isolated mitochondrial palmitate oxidation was not altered. In addition, mitochondrial FAT/CD36 content was not different in lean and obese individuals. In contrast, citrate synthase and β-hydroxyacyl-CoA dehydrogenase, common markers of total mitochondrial content, were decreased with obesity. Therefore, the decrease in mitochondrial content appeared to account for the observed reductions in whole-muscle LCFA oxidation.

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Critical Role of Intracellular RyR1 Calcium Release Channels in Skeletal Muscle Function and Disease

Frontiers in Physiology ◽

10.3389/fphys.2015.00420 ◽

2016 ◽

Vol 6 ◽

Cited By ~ 19

Author(s):

Erick O. Hernández-Ochoa ◽

Stephen J. P. Pratt ◽

Richard M. Lovering ◽

Martin F. Schneider

Keyword(s):

Skeletal Muscle ◽

Muscle Function ◽

Calcium Release ◽

Critical Role ◽

Skeletal Muscle Function ◽

Calcium Release Channels

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Inflammatory Mechanisms Associated with Skeletal Muscle Sequelae after Stroke: Role of Physical Exercise

Mediators of Inflammation ◽

10.1155/2016/3957958 ◽

2016 ◽

Vol 2016 ◽

pp. 1-19 ◽

Cited By ~ 17

Author(s):

Hélio José Coelho Junior ◽

Bruno Bavaresco Gambassi ◽

Tiego Aparecido Diniz ◽

Isabela Maia da Cruz Fernandes ◽

Érico Chagas Caperuto ◽

...

Keyword(s):

Risk Factors ◽

Skeletal Muscle ◽

Physical Exercise ◽

Muscle Atrophy ◽

Inflammatory Markers ◽

The Other ◽

Stroke Patients ◽

Beneficial Effects ◽

Anti Inflammatory

Inflammatory markers are increased systematically and locally (e.g., skeletal muscle) in stroke patients. Besides being associated with cardiovascular risk factors, proinflammatory cytokines seem to play a key role in muscle atrophy by regulating the pathways involved in this condition. As such, they may cause severe decrease in muscle strength and power, as well as impairment in cardiorespiratory fitness. On the other hand, physical exercise (PE) has been widely suggested as a powerful tool for treating stroke patients, since PE is able to regenerate, even if partially, physical and cognitive functions. However, the mechanisms underlying the beneficial effects of physical exercise in poststroke patients remain poorly understood. Thus, in this study we analyze the candidate mechanisms associated with muscle atrophy in stroke patients, as well as the modulatory effect of inflammation in this condition. Later, we suggest the two strongest anti-inflammatory candidate mechanisms, myokines and the cholinergic anti-inflammatory pathway, which may be activated by physical exercise and may contribute to a decrease in proinflammatory markers of poststroke patients.

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Role of myokines in exercise and metabolism

Journal of Applied Physiology ◽

10.1152/japplphysiol.00080.2007 ◽

2007 ◽

Vol 103 (3) ◽

pp. 1093-1098 ◽

Cited By ~ 399

Author(s):

Bente Klarlund Pedersen ◽

Thorbjörn C. A. Åkerström ◽

Anders R. Nielsen ◽

Christian P. Fischer

Keyword(s):

Skeletal Muscle ◽

Skeletal Muscles ◽

Contractile Activity ◽

Endocrine Effects ◽

Skeletal Muscle Function ◽

The Past ◽

Exercise Induced ◽

Immune Changes ◽

Muscle Contractile

During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an “exercise factor,” which could mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as “myokines.” Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named “myokines.” Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.

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The Role of Skeletal Muscle in The Pathogenesis of Altered Concentrations of Branched-Chain Amino Acids (Valine, Leucine, and Isoleucine) in Liver Cirrhosis, Diabetes, and Other Diseases

Physiological Research ◽

10.33549/physiolres.934648 ◽

2021 ◽

pp. 293-305

Author(s):

M Holeček

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Liver Cirrhosis ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

Branched Chain Amino Acids ◽

Acid Oxidation ◽

Amino Group ◽

Branched Chain

The article shows that skeletal muscle plays a dominant role in the catabolism of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) and the pathogenesis of their decreased concentrations in liver cirrhosis, increased concentrations in diabetes, and nonspecific alterations in disorders with signs of systemic inflammatory response syndrome (SIRS), such as burn injury and sepsis. The main role of skeletal muscle in BCAA catabolism is due to its mass and high activity of BCAA aminotransferase, which is absent in the liver. Decreased BCAA levels in liver cirrhosis are due to increased use of the BCAA as a donor of amino group to α-ketoglutarate for synthesis of glutamate, which in muscles acts as a substrate for ammonia detoxification to glutamine. Increased BCAA levels in diabetes are due to alterations in glycolysis, citric acid cycle, and fatty acid oxidation. Decreased glycolysis and citric cycle activity impair BCAA transamination to branched-chain keto acids (BCKAs) due to decreased supply of amino group acceptors (α-ketoglutarate, pyruvate, and oxaloacetate); increased fatty acid oxidation inhibits flux of BCKA through BCKA dehydrogenase due to increased supply of NADH and acyl-CoAs. Alterations in BCAA levels in disorders with SIRS are inconsistent due to contradictory effects of SIRS on muscles. Specifically, increased proteolysis and insulin resistance tend to increase BCAA levels, whereas activation of BCKA dehydrogenase and glutamine synthesis tend to decrease BCAA levels. The studies are needed to elucidate the role of alterations in BCAA metabolism and the effects of BCAA supplementation on the outcomes of specific diseases.

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Identification and regulation of the xenometabolite derivatives cis- and trans-3,4-methylene-heptanoylcarnitine in plasma and skeletal muscle of exercising humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00510.2019 ◽

2020 ◽

Vol 318 (5) ◽

pp. E701-E709

Author(s):

Hany F. Sobhi ◽

Xinjie Zhao ◽

Peter Plomgaard ◽

Miriam Hoene ◽

Jakob S. Hansen ◽

...

Keyword(s):

Skeletal Muscle ◽

Cyclopropane Ring ◽

Plasma Concentrations ◽

Physiological Role ◽

Hepatic Metabolism ◽

Acid Oxidation ◽

Net Uptake ◽

Cis And Trans ◽

Cis Isomer

Little is known about xenometabolites in human metabolism, particularly under exercising conditions. Previously, an exercise-modifiable, likely xenometabolite derivative, cis-3,4-methylene-heptanoylcarnitine, was reported in human plasma. Here, we identified trans-3,4-methylene-heptanoylcarnitine, and its cis-isomer, in plasma and skeletal muscle by liquid chromatography-mass spectrometry. We analyzed the regulation by exercise and the arterial-to-venous differences of these cyclopropane ring-containing carnitine esters over the hepatosplanchnic bed and the exercising leg in plasma samples obtained in three separate studies from young, lean and healthy males. Compared with other medium-chain acylcarnitines, the plasma concentrations of the 3,4-methylene-heptanoylcarnitine isomers only marginally increased with exercise. Both isomers showed a more than twofold increase in the skeletal muscle tissue of the exercising leg; this may have been due to the net effect of fatty acid oxidation in the exercising muscle and uptake from blood. The latter idea is supported by a more than twofold increased net uptake in the exercising leg only. Both isomers showed a constant release from the hepatosplanchnic bed, with an increased release of the trans-isomer after exercise. The isomers differ in their plasma concentration, with a four times higher concentration of the cis-isomer regardless of the exercise state. This is the first approach studying kinetics and fluxes of xenolipid isomers from tissues under exercise conditions, supporting the hypothesis that hepatic metabolism of cyclopropane ring-containing fatty acids is one source of these acylcarnitines in plasma. The data also provide clear evidence for an exercise-dependent regulation of xenometabolites, opening perspectives for future studies about the physiological role of this largely unknown class of metabolites.

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