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.

核因子κB（NF-κB）信号系统是免疫过程的关键调节剂，也影响与炎症和免疫反应相关的大量代谢变化。调节NF-κB的信号传导级联，与NF-κB介导的转录事件协同作用，可在多个水平上控制新陈代谢。NF-κB调节代谢过程的顶端成分，包括代谢激素（例如胰岛素和胰高血糖素），细胞主开关5'AMP激活的蛋白激酶和mTOR，以及许多代谢酶及其各自的调节剂。反之亦然，代谢酶及其产物也对NF-κB活性进行多级控制，从而建立了高度连接的调节网络。这些见解导致鉴定了非规范性IκB激酶激酶IκB激酶ɛ和TBK1，它们因营养过度而上调，因此可能是代谢综合征的合适潜在治疗靶标。干扰这两种激酶活性的抑制剂可降低小鼠模型中与肥胖有关的代谢功能障碍，最近一项临床试验的令人鼓舞的结果表明，靶向这些NF-κB途径组分可改善部分2型糖尿病患者的葡萄糖稳态。