From the Department of Internal Medicine (K.H.J.G., M.P.H.v.d.W., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), CARIM School for Cardiovascular Diseases (K.H.J.G., I.F., M.P.H.v.d.W., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Department of Clinical Epidemiology and Medical Technology Assessment (KEMTA) (I.F.), Department of General Surgery (S.S.R.), and NUTRIM School for Nutrition, Toxicology and Metabolism (S.S.R.), Maastricht University Medical Centre, The Netherlands; Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine and Biomedical Sciences, The University of Queensland, Brisbane, Australia (I.F.); and Department of Epidemiology and Biostatistics and EMGO Institute for Health and Care Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (J.M.D., G.N.).
Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2707-13. doi: 10.1161/ATVBAHA.115.306106. Epub 2015 Oct 8.
Adipose tissue inflammation contributes to the development of complications, such as insulin resistance and type 2 diabetes mellitus. We previously reported that plasma levels of N(ε)-(carboxymethyl)lysine (CML) were decreased in obese subjects resulting from CML accumulation in adipose tissue and that this CML accumulation plays an important role in adipose tissue inflammation. The objective of this study is to investigate associations between obesity (body mass index, waist circumference, and trunk fat mass), plasma CML (as an inversely correlated marker of CML accumulation in adipose tissue), and low-grade inflammation (LGI) in a large sample of individuals whose weight status ranged from normal to morbid obesity.
We studied 1270 individuals of the Cohort on Diabetes and Atherosclerosis Maastricht Study and Hoorn Study, in whom protein-bound CML levels were measured by UPLC-Tandem MS (ultra performance liquid chromatography-tandem mass spectrometry), and 6 inflammatory markers were measured with multiarrays. These inflammatory markers were compiled into an LGI score. Multiple linear regression, adjusted for covariates, showed that (1) waist circumference was inversely associated with protein-bound CML plasma levels (standardized regression coefficient [β]=-0.357 [95% confidence interval: -0.414; -0.301]); (2) protein-bound CML was inversely associated with LGI score (β=-0.073 [-0.130;-0.015]); and (3) the association between waist circumference and LGI (β=0.262 [0.203;0.321]) was attenuated after adjustment for protein-bound CML plasma levels and other potential mediators (to β=0.202 [0.138;0.266]), with CML explaining the greatest portion of the attenuation (≈12%). Further analysis with dual-energy X-ray absorptiometry measures of body composition confirmed a strong inverse association of fat mass preferentially accumulated in the trunk with protein-bound CML plasma levels, significantly explaining ≈21% of the trunk fat-LGI association.
Obesity, in particular central obesity, is characterized by greater levels of LGI but by lower levels of circulating CML; the latter significantly explaining a portion of the positive association between central obesity and inflammation.
脂肪组织炎症会导致各种并发症的发生，如胰岛素抵抗和 2 型糖尿病。我们之前曾报道，肥胖人群的血浆 N(ε)-(羧甲基)赖氨酸（CML）水平降低，这是由于脂肪组织中 CML 积累所致，而这种 CML 积累在脂肪组织炎症中起着重要作用。本研究旨在调查大量体重从正常到病态肥胖人群中，肥胖（体重指数、腰围和躯干脂肪质量）、血浆 CML（作为脂肪组织中 CML 积累的负相关标志物）和低度炎症（LGI）之间的相关性。
我们研究了 1270 名 Maastricht 糖尿病和动脉粥样硬化队列研究和 Hoorn 研究的个体，他们的血浆蛋白结合 CML 水平通过 UPLC-Tandem MS（超高效液相色谱-串联质谱）进行了测量，6 种炎症标志物通过多阵列进行了测量。这些炎症标志物被编译成一个 LGI 评分。调整协变量的多元线性回归显示，（1）腰围与蛋白结合 CML 血浆水平呈负相关（标准化回归系数 [β] = -0.357 [95%置信区间：-0.414；-0.301]）；（2）蛋白结合 CML 与 LGI 评分呈负相关（β = -0.073 [-0.130；-0.015]）；（3）腰围与 LGI 之间的关系（β=0.262 [0.203；0.321]）在调整蛋白结合 CML 血浆水平和其他潜在介质后减弱（至β=0.202 [0.138；0.266]），CML 解释了衰减的最大部分（约 12%）。使用双能 X 射线吸收法测量身体成分的进一步分析证实，躯干优先积累的脂肪质量与蛋白结合 CML 血浆水平呈强烈的负相关，显著解释了约 21%的躯干脂肪-LGI 相关性。
肥胖，特别是中心性肥胖，其特征是 LGI 水平较高，但循环 CML 水平较低；后者显著解释了中心性肥胖与炎症之间正相关的一部分。
