Reduced Adipose Tissue Inflammation Represents an Intermediate Cardiometabolic Phenotype in Obesity

• Published in: Journal of the American College of Cardiology Vol. 58; no. 3; pp. 232 - 237
• Main Authors: Farb, Melissa G., Bigornia, Sherman, Mott, Melanie, Tanriverdi, Kahraman, Morin, Kristine M., Freedman, Jane E., Joseph, Lija, Hess, Donald T., Apovian, Caroline M., Vita, Joseph A., Gokce, Noyan
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 12.07.2011; Elsevier; Elsevier Limited
• Subjects: Adult; Biological and medical sciences; Blood Glucose - analysis; Blood Pressure; Body fat; Body Mass Index; Brachial Artery - physiopathology; C-Reactive Protein - analysis; Cardiology; Cardiology. Vascular system; Cardiovascular; Cardiovascular Diseases - blood; Cardiovascular Diseases - complications; Cardiovascular Diseases - physiopathology; Cholesterol; Cholesterol - blood; endothelium; Female; Humans; Inflammation; Insulin - blood; Internal Medicine; Macrophages - pathology; Male; Medical sciences; Metabolic diseases; Metabolic Syndrome - blood; Metabolic Syndrome - complications; Obesity; Obesity - blood; Obesity - complications; Obesity - pathology; Obesity - physiopathology; Overweight - pathology; Phenotype; Subcutaneous Fat, Abdominal - pathology; Triglycerides - blood; vasculature; vasodilation; Weight control; United States > US; California; endothelium; vasculature; IL; vasodilation; mRNA; CLS; WC; MMP; inflammation; HOMA; FMD; HbA1C; hs-CRP; obesity; BMI; high-sensitivity C-reactive protein; messenger ribonucleic acid; interleukin; homeostasis model assessment; waist circumference; body mass index; crown-like structures; matrix metalloproteinase; flow-mediated dilation; glycosylated hemoglobin A1C; Obesity; Phenotype; Adipose tissue; Nutrition disorder; Inflammation; Circulatory system; Cardiology; Nutritional status
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2011.01.051

The purpose of this study was to determine whether obese individuals with reduced adipose tissue inflammation exhibit a more favorable cardiovascular risk profile. Obesity is associated with a low-grade state of chronic inflammation that might be causally related to cardiometabolic disease. 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). 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. 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.