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 cardiometabolic 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.
Key Words
endothelium
inflammation
obesity
vasculature
vasodilation
Abbreviations and Acronyms
BMI
body mass index
CLS
crown-like structures
FMD
flow-mediated dilation
HbA1C
glycosylated hemoglobin A1C
HOMA
homeostasis model assessment
hs-CRP
high-sensitivity C-reactive protein
IL
interleukin
MMP
matrix metalloproteinase
mRNA
messenger ribonucleic acid
WC
waist circumference
Cited by (0)
This work was supported by National Institutes of Health grants to Dr. Gokce (R01 HL074097 and HL084213). Dr. Vita is supported by National Institutes of Health grants HL083269, HL083801, HL081587, and HL75795. Dr. Apovian receives consulting fees from NovoNordisk, Arena, Merck, Amylin, GI Dynamics, Johnson & Johnson, Sanofi-Aventis, Orexigen, and Pfizer; and grant support from Amylin, Sanofi-Aventis, Pfizer, Orexigen, Metaproteomics, Atkins Foundation, and Arena. All other authors have reported that they have no relationships to disclose.
