title: Exercise-mimicking treatment fails to increase Fndc5 mRNA & irisin secretion in primary human myotubes.
abstract: Irisin, myokine secreted by skeletal muscle, was suggested to mediate some of exercise health benefits via "browning" of white adipose tissue. However, mounting evidence contradicts the regulatory role of exercise for muscle irisin production/secretion in humans. Thus, we explored the direct effect of exercise-mimicking treatment on irisin in human primary muscle cells in vitro. Human primary muscle cell cultures were established from lean, obese prediabetic and type-2-diabetic individuals. Complex metabolic phenotyping included assessment of insulin sensitivity (euglycemic hyperinsulinemic clamp) and adiposity content&distribution (MRI&MRS). In vitro exercise-mimicking treatment (forskolin+ionomycin) was delivered in 1-h pulse/day during differentiation. Fndc5 mRNA (qRT-PCR) and secreted irisin (ELISA) were determined in cells and media. Exercise-mimicking treatment more than doubled Pgc1α mRNA in differentiated muscle cells. Nevertheless, Fndc5 mRNA was reduced by 18% and irisin in media by 20%. Moreover, Fncd5 mRNA was increased in myotubes derived from individuals with type-2-diabetes, independent on exercise-mimicking treatment. Fndc5 mRNA in cells was positively related to fasting glycemia (p=0.0001) and negatively to whole-body insulin sensitivity (p<0.05). Collectively, our data do not support the role of exercise-related signaling pathways in irisin regulation in human skeletal muscle and confirm our previous observations on increased Fndc5 expression in muscle cells from individuals with type-2-diabetes.
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Timea
authors.initials: T
authors.lastname: Kurdiova
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Balaz
authors.affiliation: Department of Surgery, Slovak Medical University, Bratislava, Slovakia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mayer
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Denisa
authors.initials: D
authors.lastname: Maderova
authors.affiliation: Department of Radiology, University Hospital, Comenius University, Bratislava, Slovakia.
authors.forename: Vitazoslav
authors.initials: V
authors.lastname: Belan
authors.affiliation: Institute of Food Nutrition and Health, ETH Zürich, Schwerzenbach, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Wolfrum
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Ukropec
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia; Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia. Electronic address: barbara.ukropcova@savba.sk.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ukropcova
mesh_terms: D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011236:Prediabetic State / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C577593:FNDC5 protein, human; D005353:Fibronectins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D014157:Transcription Factors; D005576:Colforsin; D015759:Ionomycin
keywords: Exercise-mimicking treatment; Fndc5; Human myotubes; Irisin; Myokines; Type 2 diabetes