NFkappaB-mediated metabolic inflammation in peripheral tissues versus central nervous system.
Obesity, type 2 diabetes, and the associated metabolic syndrome are known as the aggregate products from nutritional excess, and have become huge epidemics and represent public health problems in the developed world. Yet, there exist few successful approaches for the treatment and prevention of these complex diseases, in part because they are not well understood at the molecular levels. Recent research has revealed that many nutrient- and pathogen-sensing systems can be highly integrated, positing the regulatory system of immune response at the mechanistic interface between metabolic regulation and the development of overnutrition-related diseases. The underlying molecular processes have been associated with the basis of how nutritional changes trigger atypical inflammation and how metabolic inflammation affects the signaling and functions of metabolic tissues and cells. In this endeavor, the pro-inflammatory axis consisting of the nuclear transcription factor NFkappaB and its upstream kinase IKKbeta has been identified as one critical mediator that is responsible for nutritionally-induced inflammation, and a large body of research has been documented to support the concept that IKKbeta/NFkappaB represents a general cause of various metabolic dysfunctions under overnutrition. Here, we comparatively review the tissue-specific programs and actions of IKKbeta/NFkappaB in causing and promoting overnutrition-related diseases.
Cai
Dongsheng
D
Department of Molecular Pharmacology, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. dcai@aecom.yu.edu
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology
D016328:NF-kappa B