Department of Internal Medicine, Catharina Hospital, Eindhoven, The Netherlands.
Metabolism. 2012 Dec;61(12):1787-96. doi: 10.1016/j.metabol.2012.05.015. Epub 2012 Jul 2.
To investigate the role of low-grade inflammation and insulin resistance (HOMA2-IR) in adiposity-related increases in serum complement factor 3 (C3). Although C3 has been linked to type 2 diabetes and cardiovascular diseases, and C3 levels are closely related to body fat, the underlying mechanisms explaining this association are still unknown.
Adiposity measures (including BMI, waist circumference (WC), sagittal diameter and several skinfolds), HOMA2-IR and markers of inflammation (hs-CRP, IL-6, SAA, haptoglobin, ceruloplasmin, sICAM-1) were determined in 532 individuals (62% men, mean age 59±6.9 yrs) from the Cohort on Diabetes and Atherosclerosis Maastricht study. Markers of inflammation were standardized and compiled into an averaged inflammation score. Cross-sectional associations between adiposity measures and C3 and the mediating role of low-grade inflammation and/or HOMA2-IR herein were analysed with multiple linear regression models.
Adiposity measurements were significantly associated with C3 levels, with the strongest (adjusted) associations found for WC (β=0.383; 95%CI 0.302-0.464) and sagittal diameter (β=0.412; 95%CI 0.333-0.490). Further adjustment for inflammation and HOMA2-IR attenuated these associations to β=0.115 (95%CI 0.030-0.200) and β=0.163 (95%CI 0.082-0.244) respectively. Multiple mediation analyses showed that inflammation [β=0.090 (95%CI 0.060-0.126)] and HOMA2-IR [β=0.179 (95%CI 0.128-0.236)] each explained, independently of one another, a significant portion of the association between WC and C3 (23% and 47%, respectively). Similar mediation by inflammation (19-27%) and HOMA2-IR (37-56%) was found for other adiposity measures.
Systemic low-grade inflammation and insulin resistance may represent two independent pathways by which body fat leads to elevated C3 levels.
探讨低度炎症和胰岛素抵抗（HOMA2-IR）在肥胖相关血清补体因子 3（C3）升高中的作用。虽然 C3 与 2 型糖尿病和心血管疾病有关，且 C3 水平与体脂密切相关，但解释这种关联的潜在机制尚不清楚。
在 Maastricht 糖尿病和动脉粥样硬化队列研究（Cohort on Diabetes and Atherosclerosis Maastricht study）的 532 名个体（62%为男性，平均年龄 59±6.9 岁）中，测定了肥胖指标（包括 BMI、腰围（WC）、矢状直径和多个皮褶厚度）、HOMA2-IR 和炎症标志物（hs-CRP、IL-6、SAA、触珠蛋白、铜蓝蛋白、sICAM-1）。将炎症标志物标准化并编制成平均炎症评分。采用多元线性回归模型分析肥胖指标与 C3 之间的横断面关联，以及在此过程中低度炎症和/或 HOMA2-IR 的中介作用。
肥胖测量值与 C3 水平显著相关，与 WC（β=0.383；95%CI 0.302-0.464）和矢状直径（β=0.412；95%CI 0.333-0.490）的相关性最强（校正后）。进一步调整炎症和 HOMA2-IR 后，这些相关性分别减弱为β=0.115（95%CI 0.030-0.200）和β=0.163（95%CI 0.082-0.244）。多重中介分析表明，炎症[β=0.090（95%CI 0.060-0.126）]和 HOMA2-IR[β=0.179（95%CI 0.128-0.236）]各自独立地解释了 WC 和 C3 之间的部分关联（分别为 23%和 47%）。在其他肥胖指标中也发现了类似的炎症（19-27%）和 HOMA2-IR（37-56%）介导作用。
全身低度炎症和胰岛素抵抗可能代表了脂肪组织导致 C3 水平升高的两个独立途径。
