Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. (9th January 2014)

• Record Type: Journal Article
• Authors: Kurdiova, Timea; Balaz, Miroslav; Vician, Marek; Maderova, Denisa; Vlcek, Miroslav; Valkovic, Ladislav; Srbecky, Miroslav; Imrich, Richard; Kyselovicova, Olga; Belan, Vitazoslav; Jelok, Ivan; Wolfrum, Christian; Klimes, Iwar; Krssak, Martin; Zemkova, Erika; Gasperikova, Daniela; Ukropec, Jozef; Ukropcova, Barbara
• Is Part Of: Journal of physiology. Volume 592:Number 5(2014:Mar.)
• Page Start: 1091
• Page End: 1107
• Publication Date: 2014-01-09
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/jphysiol.2013.264655
• Languages: English
• ISSNs: 0022-3751

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="tjp6003-sec-0010" sec-type="section"> <title>Key points</title> <p> <list id="tjp6003-list-0001" list-type="bullet"> <list-item> <p>Considerable controversy exists regarding the role of irisin, a putative exercise‐induced myokine, in human metabolism.</p> </list-item> <list-item> <p>We therefore studied irisin and its precursor <italic>Fndc5</italic> in obesity, type 2 diabetes and exercise.</p> </list-item> <list-item> <p>Complex clinical studies combined with cell culture work revealed that <italic>Fndc5</italic>/irisin was decreased in type 2 diabetes <italic>in vivo</italic>, but not in muscle cells <italic>in vitro</italic>, indicating that diabetes‐related factor(s) regulate <italic>Fndc5</italic>/irisin <italic>in vivo</italic>.</p> </list-item> <list-item> <p>Several attributes of type 2 diabetes, such as hyperglycaemia, triglyceridaemia, visceral adiposity and extramyocellular lipid deposition were negatively associated with adipose tissue <italic>Fndc5</italic> mRNA and circulating irisin. Moreover, mimicking diabetic status <italic>in vitro</italic> by treating muscle cells with palmitate and glucose lowered <italic>Fndc5</italic> mRNA.</p> </list-item> <list-item> <p>Neither exercise training nor an acute exercise bout modulated circulating irisin or muscle <italic>Fndc5</italic> expression. However, the associations between intensity of habitual physical activity, muscle volume, strength, contractility and circulating irisin provide a link between irisin and positive outcomes of increased physical activity.</p> </list-item> </list> </p> </sec> <sec id="tjp6003-sec-0020" sec-type="section"> <title>Abstract</title> <p>Irisin was identified as a myokine secreted by contracting skeletal muscle, possibly mediating some exercise health benefits via 'browning' of white adipose tissue. However, a controversy exists concerning irisin origin, regulation and function in humans. Thus, we have explored <italic>Fndc5</italic> gene and irisin protein in two clinical studies: (i) a cross‐sectional study (effects of type 2 diabetes (T2D) in drug‐naive men) and (ii) an intervention study (exercise effects in sedentary, overweight/obese individuals). Glucose tolerance and insulin sensitivity were assessed. Maximal aerobic capacity and muscle strength were measured before and after training. Body composition (magnetic resonance imaging), muscle and liver fat content (<sup>1</sup>H‐magnetic resonance spectroscopy (MRS)) and <italic>in vivo</italic> muscle metabolism (<sup>32</sup>P‐MRS) were determined. Skeletal muscle and subcutaneous abdominal adipose tissue samples were taken in the fasted state and during euglycaemic hyperinsulinaemia (adipose tissue) and before/after exercise training (muscle). We found that muscle <italic>Fndc5</italic> mRNA was increased in prediabetes but not T2D. <italic>Fndc5</italic> in adipose tissue and irisin in plasma were reduced in T2D by 40% and 50%, respectively. In contrast, T2D‐derived myotubes expressed/secreted the highest levels of <italic>Fndc5</italic>/irisin. Neither hyperinsulinaemia (adipose tissue/plasma) nor exercise (muscle/plasma) affected <italic>Fndc5</italic>/irisin <italic>in vivo</italic>. Circulating irisin was positively associated with muscle mass, strength and metabolism and negatively with fasting glycaemia. Glucose and palmitate decreased <italic>Fndc5</italic> mRNA in myotubes <italic>in vitro</italic>. We conclude that distinct patterns of <italic>Fndc5</italic>/irisin in muscle, adipose tissue and circulation, and concordant <italic>in vivo</italic> down‐regulation in T2D, indicate that irisin might distinguish metabolic health and disease. Moreover, <italic>Fndc5</italic>/irisin was discordantly regulated in diabetic muscle and myotubes <italic>in vitro</italic>, suggesting that whole body factors, such as glucose and fatty acids, might be important for irisin regulation. Exercise did not affect <italic>Fndc5</italic>/irisin. However, irisin was positively linked to muscle mass, strength and metabolism, pointing to common regulatory factors and/or the potential for irisin to modify muscle phenotype.</p> </sec> </abstract>