Low Inflammatory Stimulus Increases D2 Activity and Modulates Thyroid Hormone Metabolism during Myogenesis In Vitro

Area of Science:

• Muscle biology
• Endocrinology
• Inflammation research

Background:

• Thyroid hormone (TH) signaling is crucial for muscle progenitor cell differentiation.
• Inflammation can disrupt TH signaling by altering transporters, receptors, and deiodinase enzymes.
• The effect of low-grade inflammation on TH signaling during myogenesis requires further study.

Purpose of the Study:

• To investigate the impact of bacterial lipopolysaccharide (LPS)-induced inflammation on TH signaling during myogenesis.

Main Methods:

• C2C12 myoblasts were differentiated with or without 10 ng/mL LPS.
• Proinflammatory cytokine and chemokine release was measured.
• Gene expression of TH-related molecules (Slc16a2, Thra1, Dio2, Dio3, Myod1) and D2 enzymatic activity were assessed.

Main Results:

• LPS induced the release of IL-6, IL-1β, CCL2, and CXCL-1.
• LPS decreased Myod1 expression by 28% and Dio2 expression by 41% but doubled D2 enzymatic activity.
• LPS increased Slc16a2 gene expression by 38% in late differentiation stages.
• Early myogenesis was reduced, but late differentiation remained unaffected.

Conclusions:

• LPS-induced inflammation alters intracellular TH metabolism and reduces the initial myogenic stimulus.
• Despite initial impairment, late muscle differentiation is preserved, potentially due to compensatory intracellular TH activation.
• This suggests a potential recovery mechanism in myogenic differentiation under low-grade inflammatory conditions.