TSH/TSHR Signaling Suppresses Fatty Acid Synthase (FASN) Expression in Adipocytes

Area of Science:

• Endocrinology
• Molecular Biology
• Metabolic Research

Background:

• Thyroid-stimulating hormone (TSH) and its receptor (TSHR) signaling are implicated in lipid metabolism regulation within adipocytes.
• The precise molecular mechanisms underlying TSH's role in adipocyte lipid metabolism remain largely unknown.

Purpose of the Study:

• To investigate the effect of TSH on fatty acid synthase (FASN) expression in mature adipocytes.
• To elucidate the signaling pathways involved in TSH-mediated regulation of FASN.

Main Methods:

• In vitro studies using mature adipocytes treated with TSH.
• Analysis of FASN mRNA and protein levels.
• Assessment of protein kinase A (PKA), cAMP-response element binding protein (CREB), extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun NH2-terminal kinase (JNK) activation.
• Inhibition studies using specific pathway inhibitors.
• In vivo studies in C57BL/6 mice with diet-induced obesity.

Main Results:

• TSH significantly reduced FASN expression at both mRNA and protein levels in mature adipocytes.
• TSH treatment activated PKA, phosphorylated CREB, and activated ERK1/2 and JNK signaling pathways.
• Inhibition of PKA and ERK partially reversed TSH-induced FASN downregulation, while JNK inhibition had no significant effect.
• Obese mice exhibited increased TSHR and FASN expression in visceral adipose tissue, contrasting with normal thyroid TSHR expression.

Conclusions:

• TSHR activation directly inhibits FASN expression in adipocytes, likely mediated by PKA and ERK signaling pathways.
• The inhibitory function of TSHR on FASN appears to be impaired or counteracted in the context of diet-induced obesity.
• Further research is required to fully understand the mechanisms involved and the implications in obesity.