Reduced Adipose Tissue Inflammation Represents an Intermediate Cardiometabolic Phenotype in Obesity
Do obese individuals with reduced adipose tissue inflammation exhibit a more favorable cardiovascular risk profile?
With immunohistochemistry, the investigators 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. The authors compared their metabolic, vascular, and adipose tissue characteristics with lean subjects (n = 17). Group differences for continuous variables were examined with analysis of variance with Tukey post-hoc analysis, and the Kruskal-Wallis test was used for skewed variables.
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.
The authors concluded that factors in addition to absolute weight burden, such as qualitative features of adipose tissue, might be important determinants of cardiovascular disease.
This study suggests that obese individuals display more proatherogenic vascular, metabolic, and adipose tissue profiles, as compared with lean subjects. A key finding was that, for the same degree of severe obesity, individuals with reduced adipose inflammation exhibited an “intermediate” clinical phenotype with arterial function similar to normal-weight subjects. It is possible that therapeutic modulation of the adipose phenotype might represent a novel target for treatment in obesity, and requires further study.
Keywords: Waist Circumference, Biopsy, Cardiovascular Diseases, Risk Factors, Obesity, Abdominal Fat
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