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      Therapeutic effect of hybrid training of voluntary and electrical muscle contractions in middle-aged obese women with nonalcoholic fatty liver disease: a pilot trial

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          Exercise training is an effective therapy for nonalcoholic fatty liver disease (NAFLD). Hybrid training (HYB) of voluntary and electrical muscle contractions was developed to prevent disuse atrophy during space flight. HYB can be applied to obtain a strength training effect accompanying articular movement. In this pilot study, we aimed to investigate the therapeutic efficacy of HYB in NAFLD.


          A total of 15 middle-aged obese women with NAFLD who had no improvement in serum alanine aminotransferase levels and/or liver fat deposition after 12 weeks of lifestyle counseling participated in an HYB program. HYB of the quadriceps and hamstrings was conducted for 20 minutes twice a week for 24 weeks.


          NAFLD patients showed attenuated intramyocellular lipid levels in the quadriceps after the HYB intervention (−15.5%). Levels of leptin (−17.4%), tumor necrosis factor-α (−23.2%), and interleukin-6 (−30.5%) were also decreased after the intervention. HYB led to a significant body weight reduction (−4.7%), which in turn was associated with a significant decrease in serum alanine aminotransferase (−35.8%), gamma-glutamyl transpeptidase (−21.6%), ferritin (−16.0%), oxidative stress (−17.8%) levels, and insulin resistance values (−2.7%).


          In NAFLD, HYB exerts an antiobesity effect and attenuates liver dysfunction and insulin resistance in association with an increase in muscle strength and a decrease in ectopic muscle fat. Therefore, HYB has great potential as a new type of exercise therapy for liver disease in patients with NAFLD.

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          Most cited references 21

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          Muscles, exercise and obesity: skeletal muscle as a secretory organ.

          During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.
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            Muscles and their myokines.

            In the past, the role of physical activity as a life-style modulating factor has been considered as that of a tool to balance energy intake. Although it is important to avoid obesity, physical inactivity should be discussed in a much broader context. There is accumulating epidemiological evidence that a physically active life plays an independent role in the protection against type 2 diabetes, cardiovascular diseases, cancer, dementia and even depression. 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 be released from skeletal muscle during contraction and mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We have suggested that cytokines or other peptides that are produced, expressed and released by muscle fibres and exert autocrine, paracrine or endocrine effects should be classified as 'myokines'. Given that skeletal muscle is the largest organ in the human body, our discovery that contracting skeletal muscle secretes proteins sets a novel paradigm: skeletal muscle is an endocrine organ producing and releasing myokines, which work in a hormone-like fashion, exerting specific endocrine effects on other organs. Other myokines work via paracrine mechanisms, exerting local effects on signalling pathways involved in muscle metabolism. It has been suggested that myokines may contribute to exercise-induced protection against several chronic diseases.
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              Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary.


                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                04 March 2015
                : 11
                : 371-380
                [1 ]Division of Medical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
                [2 ]Division of Rehabilitation, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
                [3 ]Division of Diagnostic Radiology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan
                [4 ]Japan Society for the Promotion of Science, Tokyo, Japan
                Author notes
                Correspondence: Junichi Shoda, Division of Medical Science, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan, Tel +81 29 853 5795, Fax +81 29 853 5795, Email shodaj@ 123456md.tsukuba.ac.jp
                © 2015 Oh et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research


                exercise, muscle, nonalcoholic fatty liver disease, obesity, oxidative stress, ectopic fat


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