Science and Research

Mutual regulation of metabolic processes and proinflammatory NF-kappaB signaling

The nuclear factor kappa B (NF-kappaB) signaling system, a key regulator of immunologic processes, also affects a plethora of metabolic changes associated with inflammation and the immune response. NF-kappaB-regulating signaling cascades, in concert with NF-kappaB-mediated transcriptional events, control the metabolism at several levels. NF-kappaB 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-kappaB activity, thereby creating a highly connected regulatory network. These insights have resulted in the identification of the noncanonical IkappaB kinase kinases IkappaB kinase varepsilon 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-kappaB pathway components improves glucose homeostasis in a subset of patients with type 2 diabetes.

  • Kracht, M.
  • Muller-Ladner, U.
  • Schmitz, M. L.

Keywords

  • NF-kappaB
  • cancer
  • inflammation
  • metabolism
Publication details
DOI: 10.1016/j.jaci.2020.07.027
Journal: J Allergy Clin Immunol
Work Type: Original
Location: UGMLC
Disease Area: PALI, LC
Partner / Member: JLU
Access-Number: 32771559
See publication on PubMed

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