Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation

Mancini, Sarah J.; White, Anna D.; Bijland, Silvia; Rutherford, Claire; Graham, Delyth; Richter, Erik A.; Viollet, Benoit; Touyz, Rhian M.; Palmer, Timothy M.; Salt, Ian P.

Abstract

Inflammation of adipose tissue in obesity is associated with increased IL-1β, IL-6 and TNF-α secretion and proposed to contribute to insulin resistance. AMP-activated protein kinase (AMPK) regulates nutrient metabolism and is reported to have anti-inflammatory actions in adipose tissue, yet the mechanisms underlying this remain poorly characterised. The effect of AMPK activation on cytokine-stimulated proinflammatory signalling was therefore assessed in cultured adipocytes. AMPK activation inhibited IL-1β-stimulated CXCL10 secretion, associated with reduced interleukin-1 receptor associated kinase-4 (IRAK4) phosphorylation and downregulated MKK4/JNK and IKK/IκB/NFκB signalling. AMPK activation inhibited TNF-α-stimulated IKK/IκB/NFκB signalling but had no effect on JNK phosphorylation. The JAK/STAT3 pathway was also suppressed by AMPK after IL-6 stimulation and during adipogenesis. Adipose tissue from AMPKα1-/- mice exhibited increased JNK and STAT3 phosphorylation, supporting suppression of these distinct proinflammatory pathways by AMPK in vivo. The inhibition of multiple pro-inflammatory signalling pathways by AMPK may underlie the reported beneficial effects of AMPK activation in adipose tissue.

Citation

Mancini, S. J., White, A. D., Bijland, S., Rutherford, C., Graham, D., Richter, E. A., Viollet, B., Touyz, R. M., Palmer, T. M., & Salt, I. P. (2017). Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation. Molecular and Cellular Endocrinology, 440, 44-56. https://doi.org/10.1016/j.mce.2016.11.010

• Journal Article Type: Article
• Acceptance Date: Nov 10, 2016
• Online Publication Date: Nov 11, 2016
• Publication Date: Jan 15, 2017
• Deposit Date: Oct 30, 2018
• Publicly Available Date: Oct 30, 2018
• Journal: Molecular and Cellular Endocrinology
• Print ISSN: 0303-7207
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 440
• Pages: 44-56
• DOI: https://doi.org/10.1016/j.mce.2016.11.010
• Keywords: Biochemistry; Molecular Biology; Endocrinology
• Public URL: https://hull-repository.worktribe.com/output/1137375
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0303720716304683?via%3Dihub
• Related Public URLs: http://eprints.gla.ac.uk/131359/
• Additional Information: This article is maintained by: Elsevier; Article Title: Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation; Journal Title: Molecular and Cellular Endocrinology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.mce.2016.11.010; Content Type: article; Copyright: © 2016 The Authors. Published by Elsevier Ireland Ltd.
• Contract Date: Oct 30, 2018