Exercise-mimicking treatment fails to increase Fndc5 mRNA & irisin secretion in primary human myotubes
•Fndc5 & irisin is decreased by exercise-mimicking treatment in human myotubes.•Fndc5 mRNA is higher in myotubes derived from type-2-diabetic individuals.•Fndc5 is not related to differentiation capacity of myotubes in vitro. Irisin, myokine secreted by skeletal muscle, was suggested to mediate...
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| Veröffentlicht in: | Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2014-06, Vol.56, p.1-7 |
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| container_title | Peptides (New York, N.Y. : 1980) |
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| creator | Kurdiova, Timea Balaz, Miroslav Mayer, Alexander Maderova, Denisa Belan, Vitazoslav Wolfrum, Christian Ukropec, Jozef Ukropcova, Barbara |
| description | •Fndc5 & irisin is decreased by exercise-mimicking treatment in human myotubes.•Fndc5 mRNA is higher in myotubes derived from type-2-diabetic individuals.•Fndc5 is not related to differentiation capacity of myotubes in vitro.
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 |
| doi_str_mv | 10.1016/j.peptides.2014.03.003 |
| format | Article |
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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.</description><identifier>ISSN: 0196-9781</identifier><identifier>EISSN: 1873-5169</identifier><identifier>DOI: 10.1016/j.peptides.2014.03.003</identifier><identifier>PMID: 24642356</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Assessments ; Cells, Cultured ; Colforsin - pharmacology ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Exercise - physiology ; Exercise-mimicking treatment ; Fibronectins - genetics ; Fibronectins - metabolism ; Fibronectins - secretion ; Fndc5 ; Human ; Human myotubes ; Humans ; In vitro testing ; Insulin ; Ionomycin - pharmacology ; Irisin ; Media ; Muscle Fibers, Skeletal - drug effects ; Muscle Fibers, Skeletal - metabolism ; Muscle, Skeletal - cytology ; Muscles ; Myokines ; Obesity - genetics ; Obesity - metabolism ; Peptides ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Prediabetic State - genetics ; Prediabetic State - metabolism ; RNA, Messenger - genetics ; Secretions ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Type 2 diabetes</subject><ispartof>Peptides (New York, N.Y. : 1980), 2014-06, Vol.56, p.1-7</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-2165d0b95d2adcf3aec0bbb6c70201c90f2317f1231870d13ced08e76d3330d43</citedby><cites>FETCH-LOGICAL-c434t-2165d0b95d2adcf3aec0bbb6c70201c90f2317f1231870d13ced08e76d3330d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.peptides.2014.03.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24642356$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kurdiova, Timea</creatorcontrib><creatorcontrib>Balaz, Miroslav</creatorcontrib><creatorcontrib>Mayer, Alexander</creatorcontrib><creatorcontrib>Maderova, Denisa</creatorcontrib><creatorcontrib>Belan, Vitazoslav</creatorcontrib><creatorcontrib>Wolfrum, Christian</creatorcontrib><creatorcontrib>Ukropec, Jozef</creatorcontrib><creatorcontrib>Ukropcova, Barbara</creatorcontrib><title>Exercise-mimicking treatment fails to increase Fndc5 mRNA & irisin secretion in primary human myotubes</title><title>Peptides (New York, N.Y. : 1980)</title><addtitle>Peptides</addtitle><description>•Fndc5 & irisin is decreased by exercise-mimicking treatment in human myotubes.•Fndc5 mRNA is higher in myotubes derived from type-2-diabetic individuals.•Fndc5 is not related to differentiation capacity of myotubes in vitro.
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.</description><subject>Assessments</subject><subject>Cells, Cultured</subject><subject>Colforsin - pharmacology</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Exercise - physiology</subject><subject>Exercise-mimicking treatment</subject><subject>Fibronectins - genetics</subject><subject>Fibronectins - metabolism</subject><subject>Fibronectins - secretion</subject><subject>Fndc5</subject><subject>Human</subject><subject>Human myotubes</subject><subject>Humans</subject><subject>In vitro testing</subject><subject>Insulin</subject><subject>Ionomycin - pharmacology</subject><subject>Irisin</subject><subject>Media</subject><subject>Muscle Fibers, Skeletal - drug effects</subject><subject>Muscle Fibers, Skeletal - metabolism</subject><subject>Muscle, Skeletal - cytology</subject><subject>Muscles</subject><subject>Myokines</subject><subject>Obesity - genetics</subject><subject>Obesity - metabolism</subject><subject>Peptides</subject><subject>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</subject><subject>Prediabetic State - genetics</subject><subject>Prediabetic State - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>Secretions</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Type 2 diabetes</subject><issn>0196-9781</issn><issn>1873-5169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFu1DAQhi1ERZfCK1Q-IS4JM7HjxDeqqgWkCqSqPVuJPQEv62SxHUTfHle75VouHsn-Zkb-P8bOEWoEVB-29Z722TtKdQMoaxA1gHjBNth3ompR6ZdsA6hVpbseT9nrlLYAIKXuX7HTRirZiFZt2HT1h6L1iargg7c__fyd50hDDjRnPg1-l3heuJ9tuUzEr2dnWx5uv17wd9xHn_zME5XH7Je5YHwffRjiA_-xhmHm4WHJ60jpDTuZhl2it8d6xu6vr-4uP1c33z59uby4qawUMlcNqtbBqFvXDM5OYiAL4zgq20H5pdUwNQK7CcvZd-BQWHLQU6ecEAKcFGfs_WHuPi6_VkrZBJ8s7XbDTMuaDHaqQSkU4vNo2yL0KFX_H6gA3YJGXVB1QG1cUoo0mWMgBsE8mjNb82TOPJozIEwxVxrPjzvWMZD71_akqgAfDwCV_H57iiZZT3NJwEey2bjFP7fjLzvPrOc</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Kurdiova, Timea</creator><creator>Balaz, Miroslav</creator><creator>Mayer, Alexander</creator><creator>Maderova, Denisa</creator><creator>Belan, Vitazoslav</creator><creator>Wolfrum, Christian</creator><creator>Ukropec, Jozef</creator><creator>Ukropcova, Barbara</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7U5</scope><scope>8FD</scope><scope>L7M</scope></search><sort><creationdate>20140601</creationdate><title>Exercise-mimicking treatment fails to increase Fndc5 mRNA & irisin secretion in primary human myotubes</title><author>Kurdiova, Timea ; Balaz, Miroslav ; Mayer, Alexander ; Maderova, Denisa ; Belan, Vitazoslav ; Wolfrum, Christian ; Ukropec, Jozef ; Ukropcova, Barbara</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-2165d0b95d2adcf3aec0bbb6c70201c90f2317f1231870d13ced08e76d3330d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Assessments</topic><topic>Cells, Cultured</topic><topic>Colforsin - pharmacology</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Exercise - physiology</topic><topic>Exercise-mimicking treatment</topic><topic>Fibronectins - genetics</topic><topic>Fibronectins - metabolism</topic><topic>Fibronectins - secretion</topic><topic>Fndc5</topic><topic>Human</topic><topic>Human myotubes</topic><topic>Humans</topic><topic>In vitro testing</topic><topic>Insulin</topic><topic>Ionomycin - pharmacology</topic><topic>Irisin</topic><topic>Media</topic><topic>Muscle Fibers, Skeletal - drug effects</topic><topic>Muscle Fibers, Skeletal - metabolism</topic><topic>Muscle, Skeletal - cytology</topic><topic>Muscles</topic><topic>Myokines</topic><topic>Obesity - genetics</topic><topic>Obesity - metabolism</topic><topic>Peptides</topic><topic>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</topic><topic>Prediabetic State - genetics</topic><topic>Prediabetic State - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>Secretions</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kurdiova, Timea</creatorcontrib><creatorcontrib>Balaz, Miroslav</creatorcontrib><creatorcontrib>Mayer, Alexander</creatorcontrib><creatorcontrib>Maderova, Denisa</creatorcontrib><creatorcontrib>Belan, Vitazoslav</creatorcontrib><creatorcontrib>Wolfrum, Christian</creatorcontrib><creatorcontrib>Ukropec, Jozef</creatorcontrib><creatorcontrib>Ukropcova, Barbara</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Peptides (New York, N.Y. : 1980)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kurdiova, Timea</au><au>Balaz, Miroslav</au><au>Mayer, Alexander</au><au>Maderova, Denisa</au><au>Belan, Vitazoslav</au><au>Wolfrum, Christian</au><au>Ukropec, Jozef</au><au>Ukropcova, Barbara</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exercise-mimicking treatment fails to increase Fndc5 mRNA & irisin secretion in primary human myotubes</atitle><jtitle>Peptides (New York, N.Y. : 1980)</jtitle><addtitle>Peptides</addtitle><date>2014-06-01</date><risdate>2014</risdate><volume>56</volume><spage>1</spage><epage>7</epage><pages>1-7</pages><issn>0196-9781</issn><eissn>1873-5169</eissn><abstract>•Fndc5 & irisin is decreased by exercise-mimicking treatment in human myotubes.•Fndc5 mRNA is higher in myotubes derived from type-2-diabetic individuals.•Fndc5 is not related to differentiation capacity of myotubes in vitro.
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24642356</pmid><doi>10.1016/j.peptides.2014.03.003</doi><tpages>7</tpages></addata></record> |
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| subjects | Assessments Cells, Cultured Colforsin - pharmacology Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Exercise - physiology Exercise-mimicking treatment Fibronectins - genetics Fibronectins - metabolism Fibronectins - secretion Fndc5 Human Human myotubes Humans In vitro testing Insulin Ionomycin - pharmacology Irisin Media Muscle Fibers, Skeletal - drug effects Muscle Fibers, Skeletal - metabolism Muscle, Skeletal - cytology Muscles Myokines Obesity - genetics Obesity - metabolism Peptides Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Prediabetic State - genetics Prediabetic State - metabolism RNA, Messenger - genetics Secretions Transcription Factors - genetics Transcription Factors - metabolism Type 2 diabetes |
| title | Exercise-mimicking treatment fails to increase Fndc5 mRNA & irisin secretion in primary human myotubes |
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