Department of Biochemistry and Molecular Biology II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Biochem Biophys Res Commun. 2011 Apr 8;407(2):288-94. doi: 10.1016/j.bbrc.2011.02.137. Epub 2011 Mar 1.
Activation of the classical IκB kinases (IKKα and IKKβ) was previously shown to contribute to obesity-induced inflammation and insulin resistance. Using knockout mice, we investigated whether the related isoform IKKε plays a similar metabolic role. IKKε(-/-) mice had reduced body weight, leptin levels, as well as higher insulin sensitivity when kept on chow diet. However, inflammatory parameters, measured in liver, adipose tissue and plasma, were either unaltered or showed a trend toward up-regulation (liver NF-κB activity, TNFα and IL-1β expression). Chronic feeding of a high fat diet induced equal obesity and insulin resistance, and similarly induced inflammatory markers, in IKKε(-/-) and wild-type mice, indicating that under high caloric conditions the inflammatory and metabolic effects of IKKε deficiency were overridden. Taken together, our data indicate that IKKε does not have general pro-inflammatory properties in liver and adipose tissue, and suggest that reduced adiposity is the primary mechanism for improved insulin sensitivity in IKKε(-/-) mice on chow diet.
先前的研究表明，经典的 IκB 激酶（IKKα 和 IKKβ）的激活有助于肥胖引起的炎症和胰岛素抵抗。我们使用基因敲除小鼠研究了相关同工型 IKKε 是否具有类似的代谢作用。与野生型小鼠相比，IKKε(-/-) 小鼠在食用标准食物时体重、瘦素水平降低，胰岛素敏感性更高。然而，肝脏、脂肪组织和血浆中测量的炎症参数要么没有变化，要么表现出上调的趋势（肝脏 NF-κB 活性、TNFα 和 IL-1β 的表达）。慢性高脂饮食喂养在 IKKε(-/-) 和野生型小鼠中诱导了同等程度的肥胖和胰岛素抵抗，并同样诱导了炎症标志物的产生，这表明在高热量条件下，IKKε 缺乏的炎症和代谢作用被掩盖了。总之，我们的数据表明 IKKε 在肝脏和脂肪组织中没有普遍的促炎特性，并表明在 IKKε(-/-) 小鼠的标准饮食中，降低脂肪量是改善胰岛素敏感性的主要机制。
