Harkins Janette M, Moustaid-Moussa Naima, Chung Yong-Joo, Penner Kristen M, Pestka James J, North Colin M, Claycombe Kate J
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA.
J Nutr. 2004 Oct;134(10):2673-7. doi: 10.1093/jn/134.10.2673.
Inflammation plays a major role in the development of chronic diseases such as cardiovascular disease and Type 2 diabetes. Further, it was demonstrated that obese animals and humans have significantly higher levels of circulating proinflammatory cytokines, such as interleukin-6 (IL-6). The aim of this study was to determine whether adipose tissue could be a major source of circulating IL-6 in leptin-deficient obese (ob/ob) mice by comparing the expression of IL-6 in different tissues of ob/ob mice. Our secondary goal was to determine whether preadipocytes are the source of adipose tissue IL-6. The ob/ob mice had higher levels of plasma IL-6 (P < 0.05) and adipose tissue IL-6 mRNA (P < 0.05) compared with lean mice. Interestingly, IL-6 mRNA levels of liver and spleen were not different between ob/ob and lean mice, whereas adipose tissue IL-6 mRNA levels were higher in the ob/ob mice compared with lean mice (P < 0.05). In addition, we showed that IL-6 secretion from the adipose tissue stromal vascular fraction cells was higher than that from fully differentiated adipocytes (P < 0.001). We further demonstrated that 3T3-L1 preadipocytes had significantly higher levels of lipopolysaccharide (LPS)-stimulated IL-6 mRNA and IL-6 secretion than differentiated 3T3-L1 adipocytes. Taken together, these data suggest that adipose tissue and preadipocytes from the adipose tissue stromal vascular fraction may contribute significantly to the increased plasma IL-6 levels in ob/ob mice.
炎症在诸如心血管疾病和2型糖尿病等慢性疾病的发展过程中起着主要作用。此外,研究表明肥胖动物和人类循环中的促炎细胞因子水平显著更高,比如白细胞介素-6(IL-6)。本研究的目的是通过比较瘦素缺乏的肥胖(ob/ob)小鼠不同组织中IL-6的表达,来确定脂肪组织是否可能是ob/ob小鼠循环中IL-6的主要来源。我们的次要目标是确定前脂肪细胞是否是脂肪组织IL-6的来源。与瘦小鼠相比,ob/ob小鼠的血浆IL-6水平(P < 0.05)和脂肪组织IL-6 mRNA水平(P < 0.05)更高。有趣的是,ob/ob小鼠和瘦小鼠肝脏与脾脏的IL-6 mRNA水平没有差异,而ob/ob小鼠的脂肪组织IL-6 mRNA水平高于瘦小鼠(P < 0.05)。此外,我们发现脂肪组织基质血管成分细胞分泌的IL-6高于完全分化的脂肪细胞(P < 0.001)。我们进一步证明,3T3-L1前脂肪细胞经脂多糖(LPS)刺激后的IL-6 mRNA水平和IL-6分泌水平显著高于分化后的3T3-L1脂肪细胞。综上所述,这些数据表明脂肪组织以及来自脂肪组织基质血管成分的前脂肪细胞可能对ob/ob小鼠血浆IL-6水平升高有显著贡献。