Abstract 1559: Reduced Adipose Tissue Inflammation Represents an Intermediate Cardiometabolic Phenotype in Obesity
Obesity is associated with a low-grade state of chronic inflammation that may be causally related to cardiometabolic disease. We hypothesized that obese individuals with reduced inflammatory burden may have more favorable metabolic and vascular profiles. Using immunohistochemistry targeted to adipose tissue macrophages (ATM), we dichotomously categorized obese individuals as having inflamed fat (n=62, BMI 44±9 kg/m2) or quiescent fat (n=27, BMI 45±8) based on the presence(+) or absence(−) of ATM crown-like structures (CLS) in abdominal subcutaneous fat, as a hallmark of chronic tissue inflammation. Age and BMI were similar between the two groups (p=NS). We compared their metabolic, vascular, and adipose phenotype to lean controls (n=6; BMI=23±1 kg/m2). Inflamed CLS+ obese subjects exhibited higher plasma insulin, HOMA-IR, triglycerides, hs-CRP, SBP, and lower HDL-chol and brachial artery flow-mediated dilation (FMD) compared to the lean group (p<0.05). Also, adipose tissue mRNA expression of inflammatory genes including CD68, leptin, RANTES, MMP-9 and PAI-1 were significantly higher in the CLS+ obese group (p<0.05). In contrast, obese subjects with reduced histochemical evidence of inflammation and absent macrophage crowning (CLS−) exhibited a phenotype more similar to normal leans characterized by significantly lower plasma insulin and HOMA-IR, and reduced mRNA expression of CD68, leptin, and MMP-9 (p<0.05) as compared to CLS+ obese subjects. There were also strong trends for lower TG, CRP, and higher arterial FMD in this less inflamed obese group. Taken together, these findings suggest that systemic cardiometabolic measures to some extent mirror adipose tissue phenotype in obesity suggesting a biological connection. In addition, obese subjects with reduced adipose inflammation may have a more favorable cardiovascular risk profile despite the excess fat burden.