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, Håkan K R
AU - Gheibi, Sevda
AU - Björnholm, Marie
AU - Jørgensen, Niklas Rye
AU - Clemmensen, Christoffer
AU - Hostrup, Morten
AU - Treebak, Jonas T
AU - Krook, Anna
AU - Zierath, Juleen R
AU - Deshmukh, Atul S
N1 - Funding Information:
This work was supported by unconditional donations from the Novo Nordisk Foundation (NNF) to NNF Center for Basic Metabolic Research (NNF18CC0034900) and NNF Center for Protein Research (NNF14CC001); and supported by an EFSD/NNF Future Leaders Award to ASD (NNF19SA058976), and Swedish Research Council (2015-00165), Knut and Alice Wallenberg Foundation (2018-0094) and NNF Challenge grants (NNF14OC0011493) to J.R.Z.
Publisher Copyright:
Copyright © 2021 the American Physiological Society.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in interorgan cross talk. 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 the 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 interorgan cross talk. 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 the 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 - Exercise
KW - Exerkine
KW - Growth factor
KW - Muscle contraction
KW - Secreted factor
UR - http://www.scopus.com/inward/record.url?scp=85119155439&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.00263.2021
DO - 10.1152/ajpcell.00263.2021
M3 - Journal article
C2 - 34495765
SN - 0363-6143
VL - 321
SP - C770-C778
JO - American Journal of Physiology: Cell Physiology
JF - American Journal of Physiology: Cell Physiology
IS - 5
ER -