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ETIOPATHOGENETIC ROLE OF MYOKINES



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ETIOPATHOGENETIC ROLE OF MYOKINES 
IN EXERCISE, METABOLISM REGULATION, 
ADIPOSE TISSUE BROWNING AND DIABETES
Kovač A.Z., M.D., student, demonstrator
School of Medicine University of Zagreb, University Hospital Centre, 
KBC Rebro,
Zagreb, Croatia 
Acad. Supervisor: Prof. Z. Kovač, M.D., Ph.D., Chairman of Dept. 
Introduction.
Skeletal muscle exercise procures beneficial effects on the 
body performance and heath. Those effects are achieved through burning 
calories, muscle strengthening, improvement of exertion endurance, 
endorphin release etc. During the past couple of decades, it has become 
apparent that skeletal muscle works also as an endocrine organ, which can 
produce and secrete myokines. At the same time, skeletal muscles receive 
signals from other organs, like, hepatones, adipokines, osteokines, etc. 
Myokines are cytokines released by contracting muscle cells and they exert 
autocrine, paracrine and endocrine effects. Studies show that myokines 
regulate muscle function and mediate cross talk between skeletal muscles 
and other organs. Despite a lot of ongoing research, essence of myokines 
effects is not yet fully understood. This analysis summarizes previous 
knowledge and research of myokines and gives a broad overview of their 
actions in various physiological processes.
Methods and materials. 
This overview is based on pubmed-reached 
15 papers with references from several hundred original articles dealing 
with myokines, their biological activity and physiology. Those referenced 
papers contain quantitative and qualitative studies, whose overall 
summary is presented here as a narrative overview.
Results. 
Secretome analysis of human myocyte culture medium 
has revealed >600 of myokines. Commonly mentioned and researched 
myokines are irisin, myostatin, myonectin, IL-6, IL-15, brain-derived 
neurotrophic factor, follistatin-like 1, leukemia inhibitory factor and β‐
aminoisobutyric acid. Results of metanalytic study showed that irisin 
concentration following an acute bout of exercise increased by 15% (95% 
CI: 10.8%-19.3%). Myostatin levels have similar pattern. Immediately 


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V САТЕЛЛИТНЫЙ СИМПОЗИУМ ПО КЛИНИЧЕСКОЙ ПАТОФИЗИОЛОГИИ
after the exercise, myostatin levels increased from 2501.5 ± 78.3 pg/mL to 
2939.1 ± 839.2 pg/mL (p < 0.05). On the other side, myonectin levels may 
depend on experimental settings. For example, myonectin expression 
after 10-week exercise program decreased (58.37 ± 10.93 vs 46.59 ± 13.99), 
whereas 8-week aerobic exercise session led to significant increase of 
serum levels (0.10±0.24 vs 0.17±0.39 ng/ml) p<0.05. Each myokine acts 
in specific way in various processes and destinations. They control muscle 
adaptive processes by regulating fuel oxidation, hypertrophy, angiogenesis, 
inflammation and extracellular matrix, and induce myogenesis. Myokines 
achieve reduction of abdominal adiposity by affecting lipid and glucose 
metabolism. They improve insulin sensitivity and promote fat browning 
(switch of white adipocytes to brown fat-like, beige fat cells). Beige 
adipocytes resemble white fat cells in morphology and gene expression 
patterns during basal states, but can acquire an intermediate brown-like 
appearance marked by the expression of uncoupling protein 1, which 
uncouples oxidative phosphorylation from ATP synthesis, thereby 
resulting in heat production with a concomitant increase in energy 
expenditure.
Data in literature indicates that bone formation, endothelial cell 
function, skin structure, cognition, tumor growth and many other 
physiological aspects are also affected by myokines.

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