Myokines and adipokines: Involvement in the crosstalk between skeletal muscle and adipose tissue
Graphical abstract
Skeletal muscle-derived factors “myokines” and adipose tissue-derived factors “adipokines” exert their effects mainly in the organs of adipose tissue and/or skeletal muscle to form the muscle-adipose axis that regulates body composition.
Introduction
The prevalence of obesity has reached pandemic proportions, becoming a major public health problem in numerous developed countries where being overweight and obese results in more deaths than malnutrition. In 2014, ∼39% of adults worldwide aged ≥18 years were overweight, and 13% were obese [1]. One of the major advances in obesity research over the past decades is the discovery that adipose tissue, especially white adipose tissue (WAT), acts as an endocrine organ and modulates metabolism by signaling other organs [2].
An extensive body of in vivo and in vitro research has explored the capacity of skeletal muscle and adipose cells to produce cytokines [3], [4], [5], [6]. The concept of adipocytes as major secretory cells that release “adipokines” has more recently received greater attention owing to the development of a parallel concept in skeletal muscles. Identification of muscle as a “myokine”-producing organ has laid the foundation for a new field of research. Unfortunately, very few studies have considered the interrelation between skeletal muscle and adipose tissue, although a direct relationship between skeletal muscle mass or activity and adipose tissue mass has been indicated in some studies [4], [5], [7], [8]. Multiple determinants play a key role in this complex process. In this review, we address the effects of only myokines and adipokines on skeletal muscle and/or adipose tissue. Furthermore, particular emphasis is placed on protein and energy metabolism in myocytes and/or adipocytes.
Section snippets
Skeletal muscle
Skeletal muscle, the largest organ in the human body, is a major metabolic tissue that is responsible for approximately 85% of the insulin-stimulated glucose uptake via glucose transporter type 4 (GLUT4)-mediated transport and for lipid metabolism [9], [10]. More than a decade ago, contracting human skeletal muscle was elucidated to release significant amounts of interleukin (IL)-6 into the circulation during prolonged single-limb exercise [11], [12]. The identification of muscle as a
Myokines and their roles in skeletal muscle/adipose tissue protein and energy metabolism
Myokines have been explored to a lesser extent than adipokines. Previous studies of cytokines secreted from myocytes focused mainly on IL-6, IL-8, and IL-15 [20]. The classic and best-described member of this family is IL-6. However, during recent years, other myokines (e.g., irisin, myonectin) have been identified, revealing new scientific and technological horizons. These studies have highlighted the potential roles of myokines in mediating tissue crosstalk to control integrated physiology
Adipokines and their roles in adipose tissue/skeletal muscle protein and energy metabolism
Adipose tissue is not only an energy reserve providing free fatty acids to different tissues (e.g., skeletal muscle, liver, and heart) but also an endocrine organ with autocrine and paracrine functions due to the secretion of adipokines, such as leptin and adiponectin (Fig. 2). The different fat depots (subcutaneous vs. visceral) are heterogeneous not only in terms of metabolic capacity but also in the adipokine secretion pattern. The term adipokine is used to describe all proteins secreted
Adipo-myokines
Recent studies revealed that there is considerable overlap between myokines and adipokines. A number of cytokines (called “adipo-myokines”) secreted from skeletal muscle cells are also secreted by adipocytes [93]. The classic and best described members of this family are IL-6 and TNF-α (Table 1, Fig. 3).
Crosstalk between myokines and adipokines
Certain myokines and adipokines interact with each other. IL-6, TNF-α, and leptin are the three hormones that are modulated in a similar manner, and their communication has a further layer of complexity as TNF-α also stimulates leptin production [17]. Administration of the adipokine leptin promotes irisin-induced myogenesis, but represses the subcutaneous fat browning induced by this myokine in wild-type and ob/ob mice. Leptin administration also induces an increase in FNDC5 expression in
Proteomics/secretomics used to identify novel myokines or adipokines
Myokines and adipokines work in a hormone-like fashion, and an increasing body of evidence implies that myokines and adipokines play a critical role in body homeostasis. However, the major challenge now is to determine the characteristics of new cytokines and relate them to in vivo conditions.
Advances in proteomics have allowed for more comprehensive analyses of proteins secreted from skeletal muscle and adipose tissue. Recently, proteomic studies focusing on the secretomics (the entire
Concluding remarks and future perspectives
The evidence collected so far clearly indicates that skeletal muscle and adipose tissue function as endocrine organs producing a variety of factors to fine-tune metabolism. It is essential to further clarify the interactions among adipose depots, such as inter- and intra-muscular fats, muscles of different fiber types (types I and II), and associated signaling pathways. In this rapidly advancing age of “-omics” technologies, future studies will define new myokines and adipokines released from
Conflict of interest
The authors have no conflicts of interest to declare.
Acknowledgments
This work was jointly supported by National Basic Research Program of China (2013CB127305, 2012CB124704), Youth Innovation Promotion Association CAS (2016326), the Foundation for Innovative Research Team of ISA, and the Nature Science Foundation of Hunan Province (S2014J504I).
Feng-Na Li received her PH.D. from China Agricultural University in 2009. She is currently Associate Professor in the Animal Nutrition Department, Institute of Subtropical Agriculture, Chinese Academy of Sciences, PR China; editor of Chinese Journal of Animal Nutrition, member of the Animal Nutrition Branch of Chinese Association of Animal Science and Veterinary Medicine; current research interests: development and regulation of skeletal muscle and adipose tissues.
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Feng-Na Li received her PH.D. from China Agricultural University in 2009. She is currently Associate Professor in the Animal Nutrition Department, Institute of Subtropical Agriculture, Chinese Academy of Sciences, PR China; editor of Chinese Journal of Animal Nutrition, member of the Animal Nutrition Branch of Chinese Association of Animal Science and Veterinary Medicine; current research interests: development and regulation of skeletal muscle and adipose tissues.
Ying-Hui Li M.D. in the Animal Nutrition Department, Institute of Subtropical Agriculture, Chinese Academy of Sciences, PR China; member of the Animal Nutrition Branch of Chinese Association of Animal Science and Veterinary Medicine. Her research interest is on amino acids or plant extract and skeletal muscle development.
Ye-Hui Duan M.D. in the Animal Nutrition Department, Institute of Subtropical Agriculture, Chinese Academy of Sciences, PR China; member of the Animal Nutrition Branch of Chinese Association of Animal Science and Veterinary Medicine. Her research interest is on understanding the role of cytokines including myokines and adipokines in skeletal muscle protein synthesis and energy metabolism.
Chien-An A. Hu is Professor in Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine; he is professional member of American Society for Biochemistry and Molecular Biology and the editor of the journal Amino Acids. His scientific research is focused on the function and regulation of novel genes and proteins in health and disease.
Yu-Long Tang received his PH.D. from Zhejiang University in 2010. He is currently Associate Professor in the Animal Nutrition Department, Institute of Subtropical Agriculture, Chinese Academy of Sciences, PR China; member of the Animal Nutrition Branch of Chinese Association of Animal Science and Veterinary Medicine; current research interests: understanding the molecular mechanisms of amino acids nutrition and cell growth.
Yu-Long Yin, a professor in animal nutrition, also Chinese Academy of Engineering academicians; he is now the Editor in chief of the Animal Nutrition. His scientific research is focused on genetic and nutritional factors related to animal nutrition and health.