Abstract 882: Adipose Macrophage Infiltration Is Associated With Proinflammatory Gene Expression And Systemic Vascular Endothelial Dysfunction In Obese Subjects
Background: Inflammatory activity in fat depots and associated adipocytokine production has recently been implicated in mechanisms of insulin resistance, metabolic dysfunction, and cardiovascular disease. Recent animal studies suggest that upregulated fat macrophage (MP) activity in particular may be etiologically linked to obesity-related systemic disease.
Methods: To examine this issue in human subjects, we collected adipose tissue via abdominal subcutaneous (SC) fat biopsies in 55 consecutive obese subjects (BMI ≥ 30) and quantified macrophage populations in fat via cell-specific CD68 markers using immunohistochemistry. Extent of macrophage infiltration was related to anthropometric indexes, metabolic parameters, and brachial artery endothelial function using non-invasive high-resolution vascular ultrasound.
Results: 37 subjects (age 43 ± 11 yr, BMI 46 ± 7 kg/m2,) exhibited an inflamed fat phenotype (CD68+) by histology characterized by increased MP retention in SC reserves as compared to 18 individuals (age 44 ± 10 yr, BMI 44 ± 8 kg/m2) with a quiescent MP-sparse adipose architecture (CD68-). Endothelium-dependent, flow-mediated dilation (FMD) was significantly lower in CD68+ subjects compared to the CD68- group (7.6 ± 4.4% vs 10.5 ± 3.4%, p = 0.018), whereas endothelium-independent responses to nitroglycerin were similar (10.3 ± 2.1% vs. 12 ± 6.3% p = 0.54). Macrophage infiltration was associated with increased cytokine TNF-alpha mRNA expression in adipose tissue quantified by RT-PCR (0.12 ± 0.08 vs. 0.07 ± 0.07 au, p = 0.02). A trend for elevated plasma triglycerides was observed in the CD68+ group (140 ± 65 vs. 114 ± 46 mg/dl, p = 0.1) otherwise there were no significant group differences in total cholesterol, LDL-C, HDL-C, glucose, HgA1C, waist circumference, or statin therapy.
Conclusion: In a cohort of obese subjects, proinflammatory changes in adipose tissue including macrophage infiltration and upregulated cytokine expression are associated with systemic endothelial dysfunction. These findings suggest that inflammation in adipose tissue may be linked to systemic vascular injury and increased cardiovascular risk in obese subjects.