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Mutual regulation of metabolic processes and proinflammatory NF-κB signaling.

Authors
  • Kracht, Michael1
  • Müller-Ladner, Ulf2
  • Schmitz, M Lienhard3
  • 1 Rudolf Buchheim-Institute of Pharmacology, Justus-Liebig-University, Giessen, Germany. , (Germany)
  • 2 Department of Rheumatology and Clinical Immunology, Justus-Liebig-University, Campus Kerckhoff, Bad Nauheim, Germany. , (Germany)
  • 3 Institute of Biochemistry, Justus-Liebig-University, Giessen, Germany. Electronic address: [email protected] , (Germany)
Type
Published Article
Journal
The Journal of allergy and clinical immunology
Publication Date
Aug 06, 2020
Identifiers
DOI: 10.1016/j.jaci.2020.07.027
PMID: 32771559
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The nuclear factor kappa B (NF-κB) signaling system, a key regulator of immunologic processes, also affects a plethora of metabolic changes associated with inflammation and the immune response. NF-κB-regulating signaling cascades, in concert with NF-κB-mediated transcriptional events, control the metabolism at several levels. NF-κB modulates apical components of metabolic processes including metabolic hormones such as insulin and glucagon, the cellular master switches 5' AMP-activated protein kinase and mTOR, and also numerous metabolic enzymes and their respective regulators. Vice versa, metabolic enzymes and their products also exert multilevel control of NF-κB activity, thereby creating a highly connected regulatory network. These insights have resulted in the identification of the noncanonical IκB kinase kinases IκB kinase ɛ and TBK1, which are upregulated by overnutrition, and may therefore be suitable potential therapeutic targets for metabolic syndromes. An inhibitor interfering with the activity of both kinases reduces obesity-related metabolic dysfunctions in mouse models and the encouraging results from a recent clinical trial indicate that targeting these NF-κB pathway components improves glucose homeostasis in a subset of patients with type 2 diabetes. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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