Reduced Adipose Tissue Inflammation Represents an Intermediate Cardiometabolic Phenotype in Obesity

Abstract

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.

Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue

“…Hence, this observation suggests that the presence of type 2 diabetes inflicts adipocyte hypertrophy possibly via insufficient adipocyte differentiation, and thereby limits proper storage in the subcutaneous fat depot. Although the development of obesity and weight gain induces an enlargement of subcutaneous adipocyte cells [2], no significant increase in adipocyte cell size after 6 months of insulin treatment was observed within our study population. This may be explained by the relatively moderate weight gain observed after 6 months of insulin therapy, which was probably too small to affect adipocyte cell size.…”

“…When obesity develops, the adipose tissue undergoes distinct morphological changes including adipocyte enlargement and macrophage influx [2]. In adipose tissue in obese individuals, macrophages may be arranged in so-called crown-like structures (CLSs) that surround dysfunctional or dying adipocytes [3] and are characterised as having a more proinflammatory nature than individual macrophages dispersed throughout the adipose tissue [4].…”

Obesity and Antiplatelets-Does One Size Fit All?

“…The leptin receptor is present on platelets and potentiates aggregation in response to agonists, suggesting a potential direct link between hyperleptinemia of obesity and heightened platelet function. Farb and colleagues demonstrated that individuals with adipose tissue inflammation in subcutaneous abdominal fat biopsy samples were more likely to have impairments in vascular function, as measured by flow-mediated vasodilatation, than individuals who lacked evidence of tissue inflammation [8]. Therefore, it is reasonable to speculate that the systemic inflammation in obesity might also alter platelet function.…”

Highlights of the Year in JACC 2011

“…Local changes in adipose tissue were directly examined in a series of 3 studies. Farb et al (275) obtained abdominal subcutaneous adipose tissue from 109 overweight (BMI Ͼ25 kg/m 2 ) and 17 lean subjects. The adipose tissue showed inflammatory changes with macrophage crownlike structures in 78% of overweight subjects, whereas 22% had noninflamed fat.…”