Discovery of thymosin β4 as a human exerkine and growth factor

Alba Gonzalez-Franquesa; Ben Stocks; Melissa L Borg; Michael Kuefner; Emilie Dalbram; Thomas S Nielsen; Ankita Agrawal; Stanislava Pankratova; Alexander V Chibalin; Hakan K R Karlsson; Sevda Gheibi; Marie Björnholm; Niklas Rye Jørgensen; Christoffer Clemmensen; Jonas Thue Treebak; Morten Hostrup; Anna Krook; Juleen R Zierath; Atul Shahaji Deshmukh

doi:10.1152/ajpcell.00263.2021

Discovery of thymosin β4 as a human exerkine and growth factor

Alba Gonzalez-Franquesa, Ben Stocks, Melissa L Borg, Michael Kuefner, Emilie Dalbram, Thomas S Nielsen, Ankita Agrawal, Stanislava Pankratova, Alexander V Chibalin, Hakan K R Karlsson, Sevda Gheibi, Marie Björnholm, Niklas Rye Jørgensen, Christoffer Clemmensen, Jonas Thue Treebak, Morten Hostrup, Anna Krook, Juleen R Zierath, Atul Shahaji Deshmukh^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

16 Citations (Scopus)

65 Downloads (Pure)

Abstract

Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in inter-organ crosstalk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin β4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA-classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular cross talk.

Original language	English
Journal	American Journal of Physiology: Cell Physiology
Volume	321
Issue number	5
Pages (from-to)	C770-C778
Number of pages	9
ISSN	0363-6143
DOIs	https://doi.org/10.1152/ajpcell.00263.2021
Publication status	Published - 2021

Keywords

Faculty of Science
Muscle contraction
Exercise
Secreted factor
Exerkine
Growth factor

Access to Document

10.1152/ajpcell.00263.2021

Gonzalez-Franquesa et al_American Journal of Physiology - Cell Physiology_2021_00263_(Accepted manuscript)Accepted author manuscript, 3.17 MBLicence: Unspecified

Cite this

Gonzalez-Franquesa, A., Stocks, B., Borg, M. L., Kuefner, M., Dalbram, E., Nielsen, T. S., Agrawal, A., Pankratova, S., Chibalin, A. V., Karlsson, H. K. R., Gheibi, S., Björnholm, M., Jørgensen, N. R., Clemmensen, C., Treebak, J. T., Hostrup, M., Krook, A., Zierath, J. R., & Deshmukh, A. S. (2021). Discovery of thymosin β4 as a human exerkine and growth factor. American Journal of Physiology: Cell Physiology, 321(5), C770-C778. https://doi.org/10.1152/ajpcell.00263.2021

Discovery of thymosin β4 as a human exerkine and growth factor. / Gonzalez-Franquesa, Alba; Stocks, Ben; Borg, Melissa L; Kuefner, Michael; Dalbram, Emilie ; Nielsen, Thomas S; Agrawal, Ankita; Pankratova, Stanislava; Chibalin, Alexander V; Karlsson, Hakan K R; Gheibi, Sevda; Björnholm, Marie; Jørgensen, Niklas Rye ; Clemmensen, Christoffer ; Treebak, Jonas Thue ; Hostrup, Morten; Krook, Anna; Zierath, Juleen R ; Deshmukh, Atul Shahaji.

In: American Journal of Physiology: Cell Physiology, Vol. 321, No. 5, 2021, p. C770-C778.

Research output: Contribution to journal › Journal article › Research › peer-review

Gonzalez-Franquesa, A, Stocks, B, Borg, ML, Kuefner, M, Dalbram, E , Nielsen, TS, Agrawal, A, Pankratova, S, Chibalin, AV, Karlsson, HKR, Gheibi, S, Björnholm, M, Jørgensen, NR , Clemmensen, C , Treebak, JT , Hostrup, M, Krook, A, Zierath, JR & Deshmukh, AS 2021, 'Discovery of thymosin β4 as a human exerkine and growth factor', American Journal of Physiology: Cell Physiology, vol. 321, no. 5, pp. C770-C778. https://doi.org/10.1152/ajpcell.00263.2021

Gonzalez-Franquesa, Alba ; Stocks, Ben ; Borg, Melissa L ; Kuefner, Michael ; Dalbram, Emilie ; Nielsen, Thomas S ; Agrawal, Ankita ; Pankratova, Stanislava ; Chibalin, Alexander V ; Karlsson, Hakan K R ; Gheibi, Sevda ; Björnholm, Marie ; Jørgensen, Niklas Rye ; Clemmensen, Christoffer ; Treebak, Jonas Thue ; Hostrup, Morten ; Krook, Anna ; Zierath, Juleen R ; Deshmukh, Atul Shahaji. / Discovery of thymosin β4 as a human exerkine and growth factor. In: American Journal of Physiology: Cell Physiology. 2021 ; Vol. 321, No. 5. pp. C770-C778.

@article{863e5e4020ee4b3fa8bbecd66cee3f59,

title = "Discovery of thymosin β4 as a human exerkine and growth factor",

abstract = "Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in inter-organ crosstalk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin β4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA-classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular cross talk.",

keywords = "Faculty of Science, Muscle contraction, Exercise, Secreted factor, Exerkine, Growth factor",

author = "Alba Gonzalez-Franquesa and Ben Stocks and Borg, {Melissa L} and Michael Kuefner and Emilie Dalbram and Nielsen, {Thomas S} and Ankita Agrawal and Stanislava Pankratova and Chibalin, {Alexander V} and Karlsson, {Hakan K R} and Sevda Gheibi and Marie Bj{\"o}rnholm and J{\o}rgensen, {Niklas Rye} and Christoffer Clemmensen and Treebak, {Jonas Thue} and Morten Hostrup and Anna Krook and Zierath, {Juleen R} and Deshmukh, {Atul Shahaji}",

note = "CURIS 2021 NEXS 320",

year = "2021",

doi = "10.1152/ajpcell.00263.2021",

language = "English",

volume = "321",

pages = "C770--C778",

journal = "American Journal of Physiology: Cell Physiology",

issn = "0363-6143",

publisher = "American Physiological Society",

number = "5",

}

TY - JOUR

T1 - Discovery of thymosin β4 as a human exerkine and growth factor

AU - Gonzalez-Franquesa, Alba

AU - Stocks, Ben

AU - Borg, Melissa L

AU - Kuefner, Michael

AU - Dalbram, Emilie

AU - Nielsen, Thomas S

AU - Agrawal, Ankita

AU - Pankratova, Stanislava

AU - Chibalin, Alexander V

AU - Karlsson, Hakan K R

AU - Gheibi, Sevda

AU - Björnholm, Marie

AU - Jørgensen, Niklas Rye

AU - Clemmensen, Christoffer

AU - Treebak, Jonas Thue

AU - Hostrup, Morten

AU - Krook, Anna

AU - Zierath, Juleen R

AU - Deshmukh, Atul Shahaji

N1 - CURIS 2021 NEXS 320

PY - 2021

Y1 - 2021

N2 - Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in inter-organ crosstalk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin β4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA-classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular cross talk.

AB - Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in inter-organ crosstalk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin β4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA-classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular cross talk.

KW - Faculty of Science

KW - Muscle contraction

KW - Exercise

KW - Secreted factor

KW - Exerkine

KW - Growth factor

U2 - 10.1152/ajpcell.00263.2021

DO - 10.1152/ajpcell.00263.2021

M3 - Journal article

C2 - 34495765

VL - 321

SP - C770-C778

JO - American Journal of Physiology: Cell Physiology

JF - American Journal of Physiology: Cell Physiology

SN - 0363-6143

IS - 5

ER -