ASSESSMENT OF MACROPHAGE INFLAMMATORY ACTIVITY ON VISCERAL ADIPOSE TISSUE IN HIGH-FAT DIET-INDUCED OBESE MICE BY 18F-FDG PET/CT

초록

Objective: Obesity induced inflamed visceral adipose tissue (VAT) secretes pro-inflammatory cytokines thereby promoting systemic inflammation and insulin resistance which further exacerbate obesity-related cardiovascular disease (CVD). Macrophages are the key players in the development of obesity-associated VAT inflammation. Extensive clinical studies have reported that 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) can be used to evaluate the macrophage inflammatory activity on VAT in human beings. However, due to difficulty in human VAT biopsy, pathologic correlations were lacking and there was a few study on preclinical animal models. Here, we investigated whether 18F-FDG PET/CT could reflect the macrophage inflammatory activity on VAT in high-fat diet-induced obese mice. Design and method: Obese animal models were induced by a high-fat diet (60% fat) for 20 weeks using the male C57BL/6 mice. Insulin tolerance test was performed to evaluate the status of insulin resistance and C-reactive protein (CRP) was measured to assess the status of systemic inflammation. All animals underwent 18F-FDG PET/CT before sacrifice. Macrophage inflammatory activity was evaluated using the maximum standardized uptake value (SUVmax). Flow cytometry-, histological-, and molecular analyses were performed on harvested VAT. Results: All obese animals showed insulin resistance which resembled the human metabolic syndrome, a key pathophysiological process that contributes to increase CVD risk. VAT SUVmax was increased in obese mice and significantly correlated with the levels of CRP. Furthermore, VAT from obese mice showed increased macrophage infiltration, compared to normal mice. Conclusions: 18F-FDG PET/CT could visualize and evaluate the macrophage inflammatory activity on obesity-driven inflamed VAT in obese mice model. Our preclinical study strongly supports the clinical application of 18F-FDG PET/CT in the assessment of VAT inflammation to patients who are vulnerable to CVD.