Nam Heesun, Ferguson Bradley S, Stephens Jacqueline M, Morrison Ron F
Department of Nutrition, The University of North Carolina, Greensboro, NC 27402, USA.
Biochim Biophys Acta. 2013 Jan;1832(1):11-9. doi: 10.1016/j.bbadis.2012.08.011. Epub 2012 Aug 23.
Mounting evidence has established a role for chronic inflammation in the development of obesity-induced insulin resistance, as genetic ablation of pro-inflammatory cytokines and chemokines elevated in obesity improves insulin signaling in vitro and in vivo. Recent evidence further highlights interleukin (IL)-12 family cytokines as prospective inflammatory mediators linking obesity to insulin resistance. In this study, we present empirical evidence demonstrating that IL-12 family related genes are expressed and regulated in insulin-responsive tissues under conditions of obesity. First, we report that respective mRNAs for each of the known members of this cytokine family are expressed within detectable ranges in WAT, skeletal muscle, liver and heart. Second, we show that these cytokines and their cognate receptors are divergently regulated with genetic obesity in a tissue-specific manner. Third, we demonstrate that select IL-12 family cytokines are regulated in WAT in a manner that is dependent on the developmental stage of obesity as well as the inflammatory progression associated with obesity. Fourth, we report that respective mRNAs for IL-12 cytokines and receptors are also expressed and divergently regulated in cultured adipocytes under conditions of inflammatory stress. To our knowledge, this report is the first study to systemically evaluated mRNA expression of all IL-12 family cytokines and receptors in any tissue under conditions of obesity highlighting select family members as potential mediators linking excess nutrient intake to metabolic diseases such as insulin resistance, diabetes and heart disease.
越来越多的证据表明，慢性炎症在肥胖诱导的胰岛素抵抗发展过程中发挥作用，因为肥胖时升高的促炎细胞因子和趋化因子的基因缺失可改善体外和体内的胰岛素信号传导。最近的证据进一步强调白细胞介素（IL）-12家族细胞因子是将肥胖与胰岛素抵抗联系起来的潜在炎症介质。在本研究中，我们提供了经验证据，证明在肥胖条件下，IL-12家族相关基因在胰岛素反应性组织中表达并受到调控。首先，我们报告该细胞因子家族每个已知成员的各自mRNA在白色脂肪组织、骨骼肌、肝脏和心脏中在可检测范围内表达。其次，我们表明这些细胞因子及其同源受体在遗传性肥胖中以组织特异性方式受到不同调控。第三，我们证明特定的IL-12家族细胞因子在白色脂肪组织中的调控方式取决于肥胖的发育阶段以及与肥胖相关的炎症进展。第四，我们报告在炎症应激条件下，培养的脂肪细胞中也表达并不同调控IL-12细胞因子和受体的各自mRNA。据我们所知，本报告是第一项在肥胖条件下系统评估任何组织中所有IL-12家族细胞因子和受体mRNA表达的研究，突出了特定家族成员作为将过量营养摄入与代谢疾病（如胰岛素抵抗、糖尿病和心脏病）联系起来的潜在介质。
