Cai Dongsheng
Department of Molecular Pharmacology, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Cell Cycle. 2009 Aug 15;8(16):2542-8. doi: 10.4161/cc.8.16.9386. Epub 2009 Aug 29.
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.
肥胖、2型糖尿病及相关代谢综合征是营养过剩的综合产物，在发达国家已成为大规模流行疾病并构成公共卫生问题。然而，针对这些复杂疾病的治疗和预防方法鲜有成功案例，部分原因在于人们尚未在分子层面充分理解这些疾病。最近的研究表明，许多营养和病原体感知系统能够高度整合，在代谢调节与营养过剩相关疾病发展的机制界面上建立免疫反应调节系统。潜在的分子过程与营养变化如何引发非典型炎症以及代谢性炎症如何影响代谢组织和细胞的信号传导及功能的基础相关。在此过程中，由核转录因子NFκB及其上游激酶IKKβ组成的促炎轴已被确定为营养诱导炎症的关键介质，大量研究已证实IKKβ/NFκB是营养过剩情况下各种代谢功能障碍的普遍原因这一概念。在此，我们比较性地综述IKKβ/NFκB在引发和促进营养过剩相关疾病方面的组织特异性程序及作用。
