Reduced Adipose Tissue Inflammation Represents an Intermediate Cardiometabolic Phenotype in Obesity
Reduced Adipose Tissue Inflammation Represents an Intermediate Cardiometabolic Phenotype in Obesity
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DOI：
10.1016/j.jacc.2011.01.051
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发表时间：
2011-07-12
影响因子：
24
通讯作者：
Gokce, Noyan
中科院分区：
文献类型：
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作者：
Farb, Melissa G.;Bigornia, Sherman;Gokce, Noyan
目的探讨脂肪组织炎症减轻的肥胖者是否表现出更有利的心血管危险状态。背景肥胖与慢性炎症的低度状态有关，这可能与心脏代谢疾病有关。方法采用免疫组织化学方法，根据腹部皮下脂肪活检标本中巨噬细胞冠状结构(CLS)的存在(+)或缺失(-)，将肥胖者分为炎性脂肪(n=78)和非炎性脂肪(n=31)。结果炎症性CLS+肥胖者的血浆胰岛素、稳态模型评估、甘油三酯、血糖、血压、高敏C反应蛋白、低密度脂蛋白胆固醇、低密度脂蛋白胆固醇、肱动脉血流介导的扩张均高于瘦肉者(p<；0.05)。CLS+组炎症基因CD68、瘦素、基质金属蛋白酶-9、CD163、CD8A的脂肪信使核糖核酸表达明显增强，血管内皮生长因子表达降低(p<；0.05)。相反，与瘦身受试者一样，患有非炎性脂肪的肥胖受试者表现出混合的临床表型，表现为较低的胰岛素抵抗、较低的致动脉粥样硬化基因表达和保存的血管功能。在调整年龄和性别的多元线性回归中，CLS状态(β=-0.28，p=0.008)和腰围(β=-0.25，p=0.03)是血流介导的扩张的独立预测因素。结论这些发现支持除了绝对体重负荷之外的因素，如脂肪组织的质量特征，可能是心血管疾病的重要决定因素。脂肪表型的治疗性调节可能是肥胖症治疗的目标。(J Am Coll心脏ol 2011；58：232-7)(C)2011年，美国心脏病学会基金会
Objectives The purpose of this study was to determine whether obese individuals with reduced adipose tissue inflammation exhibit a more favorable cardiovascular risk profile.Background Obesity is associated with a low-grade state of chronic inflammation that might be causally related to cardio-metabolic disease.Methods With immunohistochemistry, we categorized obese individuals dichotomously as having inflamed fat (n = 78) or noninflamed fat (n = 31) on the basis of the presence (+) or absence (-) of macrophage crown-like structures (CLS) in subcutaneous abdominal fat biopsy samples. We compared their metabolic, vascular, and adipose tissue characteristics with lean subjects (n = 17).Results Inflamed CLS+ obese individuals displayed higher plasma insulin, homeostasis model assessment, triglycerides, glucose, blood pressure, high-sensitivity C-reactive protein, low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, and brachial artery flow-mediated dilation compared with lean subjects (p < 0.05). Adipose messenger ribonucleic acid expression of inflammatory genes including CD68, leptin, matrix metalloproteinase-9, CD163, and CD8A were significantly greater and vascular endothelial growth factor was lower in the CLS+ group (p < 0.05). In contrast, obese subjects with noninflamed fat exhibited a mixed clinical phenotype with lower insulin resistance, reduced proatherogenic gene expression, and preserved vascular function as in lean subjects. In multiple linear regression adjusting for age and sex, CLS status (beta = -0.28, p = 0.008) and waist circumference (beta = -0.25, p = 0.03) were independent predictors of flow-mediated dilation.Conclusions These findings lend support to the novel concept that factors in addition to absolute weight burden, such as qualitative features of adipose tissue, might be important determinants of cardiovascular disease. Therapeutic modulation of the adipose phenotype might represent a target for treatment in obesity. (J Am Coll Cardiol 2011;58:232-7) (C) 2011 by the American College of Cardiology Foundation