AnneMarie Gagnon1, Melanie L Langille1, Seham Chaker1, Tayze T Antunes1, Jason Durand1, Alexander Sorisky2. 1. Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada. 2. Chronic Disease Program, Ottawa Hospital Research Institute, Departments of Medicine and of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: asorisky@ohri.ca.
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.
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 humanTSH 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.
Authors: A Tropeano; D Corica; S Curatola; A Li Pomi; C Casto; A Alibrandi; G Pepe; T Aversa; M Wasniewska Journal: J Endocrinol Invest Date: 2022-08-20 Impact factor: 5.467