Reduced Adipose Tissue Inflammation Represents an Intermediate Cardiometabolic Phenotype in Obesity

Objective 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 may be causally related to cardiometabolic disease. Methods Using immunohistochemistry, we categorized obese individuals dichotomously as having inflamed fat (n=78) or non-inflamed fat (n=31) based on 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 to lean subjects (n=17). Results Inflamed CLS+ obese individuals displayed higher plasma insulin, HOMA, triglycerides, glucose, blood pressure, hs-CRP, LDL-C, and lower HDL-C and brachial artery flow-mediated dilation (FMD) compared to leans (p<0.05). Adipose mRNA expression of inflammatory genes including CD68, leptin, MMP-9, CD163, and CD8A were significantly greater and VEGF lower in the CLS+ group (p<0.05). In contrast, obese subjects with non-inflamed 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 gender, CLS status (beta = -0.28, p=0.008) and waist circumference (beta = -0.25, p =0.03) were independent predictors of FMD. Conclusion These findings lend support to the novel concept that factors in addition to absolute weight burden, such as qualitative features of adipose tissue, may be important determinants of cardiovascular disease. Therapeutic modulation of the adipose phenotype may represent a target for treatment in obesity.