AI Article Synopsis
- Adipose tissue can respond to thyroid-stimulating hormone (TSH), which increases lipolysis and the release of the cytokine IL-6 in fat cells.
- The study aimed to investigate how TSH activates two signaling pathways: protein kinase A (PKA) and IKK-β, and whether it also stimulates other cytokines.
- Results showed that TSH boosts certain enzyme activities and promotes the expression of another cytokine, MCP-1, highlighting TSH's role as a pro-inflammatory agent in fat cells.
Article Abstract
Objective: Adipose tissue is an extra-thyroidal thyroid-stimulating hormone (TSH) target. Increases in lipolysis and in expression and release of interleukin-6 (IL-6) occur in TSH-stimulated adipocytes, and levels of circulating free fatty acids and IL-6 rise following TSH administration to patients with previous thyroidectomy and radioablation for thyroid cancer. Our first objective was to compare how TSH stimulates protein kinase A (PKA) and inhibitor of κB (IκB) kinase (IKK)-β. Our second objective was to investigate whether TSH induces other cytokines besides IL-6.
Methods: TSH stimulation of either CHO cells expressing human TSH receptor or human abdominal subcutaneous differentiated adipocytes.
Results: Signaling studies showed TSH increased NADPH oxidase activity, and either diphenyleneiodonium (oxidase inhibitor) or N-acetyl cysteine (scavenger of reactive oxygen species) reduced IKKβ phosphorylation. Phosphorylation of protein kinase C-δ, an upstream regulator of NADPH oxidase, was increased by TSH, and rottlerin (PKCδ inhibitor) reduced TSH-stimulated IKKβ phosphorylation. TSH upregulated monocyte chemoattractant protein-1 (MCP-1) mRNA expression and the release of MCP-1 protein in human abdominal differentiated adipocytes. H89 (PKA inhibitor) and sc-514 (IKKβ inhibitor) each blocked TSH-stimulated MCP-1 mRNA expression and protein release, suggesting PKA and IKKβ participate in this pathway.
Conclusions: These data provide new information about TSH signaling in human differentiated adipocytes, and add to the evidence that TSH is a pro-inflammatory stimulus of adipocytes.
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| http://dx.doi.org/10.1016/j.metabol.2014.02.015 | DOI Listing |
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