TY - JOUR
T1 - Low Inflammatory Stimulus Increases D2 Activity and Modulates Thyroid Hormone Metabolism during Myogenesis In Vitro
AU - de Oliveira, Thamires Siqueira
AU - Shimabukuro, Marilia Kimie
AU - Monteiro, Victoria Regina Siqueira
AU - Andrade, Cherley Borba Vieira
AU - Boelen, Anita
AU - Wajner, Simone Magagnin
AU - Maia, Ana Luiza
AU - Ortiga-Carvalho, Tania Maria
AU - Bloise, Flavia Fonseca
N1 - Funding Information: This research was funded by Brazilian Society of Endocrinology and Metabolism (SBEM)— Thyroid Department, Brazilian National Council for Scientific and Technological Development (CNPq; T.M.O.-C.: 304667/2016-1, 422441/2016-3), Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ, T.M.O.-C.: 202.798/2018; and F.F.B.: E-26/010.002643/2019), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior —Brazil (CAPES)—Finance Code 001. T.S.d.O. was a recipient of the master program “FAPERJ nota 10” (FAPERJ). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Thyroid hormone (TH) signaling controls muscle progenitor cells differentiation. How-ever, inflammation can alter muscle TH signaling by modulating the expression of TH transporters (Slc16a2), receptors (Thra1), and deiodinase enzymes (Dio2 and Dio3). Thus, a proinflammatory environment could affect myogenesis. The role of a low-grade inflammatory milieu in TH signaling during myogenesis needs further investigation. Herein, we aimed to study the impact of the bacterial lipopolysaccharide (LPS)-induced inflammatory stimulus on the TH signaling during myogenesis. C2C12 myoblasts differentiation was induced without (CTR) or with 10 ng/mL LPS presence. The my-oblasts under LPS stimulus release the proinflammatory cytokines (IL-6 and IL-1β) and chemokines (CCL2 and CXCL-1). LPS decreases Myod1 expression by 28% during the initial myogenesis, thus reducing the myogenic stimulus. At the same time, LPS reduced the expression of Dio2 by 41% but doubled the D2 enzymatic activity. The late differentiation was not affected by inflammatory milieu, which only increased the Slc16a2 gene expression by 38%. LPS altered the intracellular metabolism of TH and reduced the initial myogenic stimulus. However, it did not affect late differentiation. Increased intracellular TH activation may be the compensatory pathway involved in the recovery of myogenic differentiation under a low-grade inflammatory milieu.
AB - Thyroid hormone (TH) signaling controls muscle progenitor cells differentiation. How-ever, inflammation can alter muscle TH signaling by modulating the expression of TH transporters (Slc16a2), receptors (Thra1), and deiodinase enzymes (Dio2 and Dio3). Thus, a proinflammatory environment could affect myogenesis. The role of a low-grade inflammatory milieu in TH signaling during myogenesis needs further investigation. Herein, we aimed to study the impact of the bacterial lipopolysaccharide (LPS)-induced inflammatory stimulus on the TH signaling during myogenesis. C2C12 myoblasts differentiation was induced without (CTR) or with 10 ng/mL LPS presence. The my-oblasts under LPS stimulus release the proinflammatory cytokines (IL-6 and IL-1β) and chemokines (CCL2 and CXCL-1). LPS decreases Myod1 expression by 28% during the initial myogenesis, thus reducing the myogenic stimulus. At the same time, LPS reduced the expression of Dio2 by 41% but doubled the D2 enzymatic activity. The late differentiation was not affected by inflammatory milieu, which only increased the Slc16a2 gene expression by 38%. LPS altered the intracellular metabolism of TH and reduced the initial myogenic stimulus. However, it did not affect late differentiation. Increased intracellular TH activation may be the compensatory pathway involved in the recovery of myogenic differentiation under a low-grade inflammatory milieu.
KW - C2C12
KW - bacterial lipopolysaccharide
KW - deiodinase
KW - inflammation
KW - myoblast
KW - myogenic differentiation
KW - triiodothyronine
UR - http://www.scopus.com/inward/record.url?scp=85130198987&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/metabo12050416
DO - https://doi.org/10.3390/metabo12050416
M3 - Article
C2 - 35629920
SN - 2218-1989
VL - 12
JO - Metabolites
JF - Metabolites
IS - 5
M1 - 416
ER -