Department of Adipose Tissue Biology, Institute of Physiology of the Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic.
Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.
Int J Obes (Lond). 2014 Feb;38(2):216-23. doi: 10.1038/ijo.2013.108. Epub 2013 Jun 12.
Resolution of low-grade inflammation of white adipose tissue (WAT) is one of the keys for amelioration of obesity-associated metabolic dysfunctions. We focused on the identification of adipokines, which could be involved at the early stages of resolution of WAT inflammation.
Male C57BL/6J mice with obesity induced in response to a 22-week feeding corn oil-based high-fat (cHF) diet were divided into four groups and were fed with, for 2 weeks, control cHF diet or cHF-based diets supplemented with: (i) concentrate of n-3 long-chain polyunsaturated fatty acids, mainly eicosapentaenoic and docosahexaenoic acids (cHF+F); (ii) thiazolidinedione drug rosiglitazone (cHF+TZD); and (iii) both compounds (cHF+F+TZD).
The short-term combined intervention exerted additive effect in the amelioration of WAT inflammation in obese mice, namely in the epididymal fat, even in the absence of any changes in either adipocyte volume or fat mass. The combined intervention elicited hypolipidaemic effect and induced adiponectin, whereas the responses to single interventions (cHF+F, cHF+TZD) were less pronounced. In addition, analysis in WAT lysates using protein arrays revealed that the levels of a small set of adipose tissue-related proteins, namely macrophage inflammatory protein 1γ, endoglin, vascular cell adhesion molecule 1 and interleukin 1 receptor antagonist, changed in response to the anti-inflammatory interventions and were strongly reduced in the cHF+F+TZD mice. These results were verified using both the analysis of gene expression and enzyme-linked immunosorbent analysis in WAT lysates. In contrast with adiponectin, which showed changing plasma levels in response to dietary interventions, the levels of the above proteins were affected only in WAT.
We identified several adipose tissue-related proteins, which are locally involved in resolution of low-grade inflammation and remodelling of WAT.
解决白色脂肪组织(WAT)低度炎症是改善肥胖相关代谢功能障碍的关键之一。我们专注于鉴定可能参与 WAT 炎症早期消退的脂肪因子。
雄性 C57BL/6J 肥胖小鼠通过 22 周玉米油基高脂肪(cHF)饮食喂养诱导肥胖,分为四组,喂养 2 周:对照 cHF 饮食或补充以下 cHF 饮食:(i)浓缩 n-3 长链多不饱和脂肪酸,主要为二十碳五烯酸和二十二碳六烯酸(cHF+F);(ii)噻唑烷二酮类药物罗格列酮(cHF+TZD);和(iii)两者的混合物(cHF+F+TZD)。
短期联合干预对肥胖小鼠 WAT 炎症的改善具有附加作用,即附睾脂肪组织,即使在脂肪细胞体积或脂肪质量没有任何变化的情况下也是如此。联合干预引起了血脂降低作用并诱导了脂联素,而单一干预(cHF+F、cHF+TZD)的反应则不太明显。此外,使用蛋白质芯片对 WAT 裂解物进行分析表明,一小部分与脂肪组织相关的蛋白质水平发生了变化,即巨噬细胞炎症蛋白 1γ、内胚层蛋白、血管细胞黏附分子 1 和白细胞介素 1 受体拮抗剂,对抗炎干预有反应,并在 cHF+F+TZD 小鼠中强烈降低。这些结果通过 WAT 裂解物中的基因表达和酶联免疫吸附分析得到验证。与响应饮食干预而改变的血浆水平的脂联素不同,这些蛋白质的水平仅在 WAT 中受到影响。
我们鉴定了几种与脂肪组织相关的蛋白质,它们局部参与解决低度炎症和 WAT 的重塑。