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 -