Skurk Thomas, Kolb Hubert, Müller-Scholze Sylvia, Röhrig Karin, Hauner Hans, Herder Christian
Else Kröner-Fresenius Center for Nutritional Medicine, Technical University Munich, D-85350 Weihenstephan, Germany.
Eur J Endocrinol. 2005 Jun;152(6):863-8. doi: 10.1530/eje.1.01897.
Interleukin (IL)-18, an important mediator of innate immunity and strong risk factor for the development of cardiovascular disease, was shown recently to be elevated in obesity. The aim of our study was to investigate whether human adipocytes produce IL-18.
Human adipose tissue was obtained from lean women undergoing elective plastic surgery and from obese individuals undergoing laparoscopic surgery (gastric banding). Preadipocytes from mammary adipose tissue were isolated and differentiated under defined adipogenic conditions. IL-18 expression was analyzed by real-time reverse transcriptase PCR, ELISA and immunocytochemistry.
Human preadipocytes of all differentiation stages spontaneously secreted IL-18. In parallel significant amounts of IL-18 mRNA were detected. Freshly isolated mature adipocytes from subcutaneous and omental depots also released IL-18. IL-18 release from adipocytes from obese donors was about 3-fold higher compared to adipocytes from non-obese donors.
We conclude that human adipose tissue produces IL-18 and thereby contributes to systemic IL-18 concentrations. This finding supports the concepts that adipocytes behave as primitive immune cells and that IL-18 may mediate some of the detrimental complications of obesity such as cardiovascular disease and type 2 diabetes.
白细胞介素(IL)-18是天然免疫的重要介质,也是心血管疾病发生的强大风险因素,最近研究表明其在肥胖人群中水平升高。我们研究的目的是调查人类脂肪细胞是否产生IL-18。
从接受择期整形手术的瘦女性以及接受腹腔镜手术(胃束带术)的肥胖个体获取人类脂肪组织。分离乳腺脂肪组织中的前脂肪细胞,并在特定的成脂条件下进行分化。通过实时逆转录聚合酶链反应、酶联免疫吸附测定和免疫细胞化学分析IL-18的表达。
所有分化阶段的人类前脂肪细胞均自发分泌IL-18。同时检测到大量的IL-18信使核糖核酸。从皮下和网膜部位新鲜分离的成熟脂肪细胞也释放IL-18。肥胖供体的脂肪细胞释放的IL-18比非肥胖供体的脂肪细胞高出约3倍。
我们得出结论,人类脂肪组织产生IL-18,从而导致全身IL-18浓度升高。这一发现支持了脂肪细胞表现为原始免疫细胞以及IL-18可能介导肥胖的一些有害并发症(如心血管疾病和2型糖尿病)的观点。