Assessment of macrophage inflammatory activity on visceral adipose tissue in high-fat diet-induced obese mice by 18F- FDG PET/CT

초록

Background and Aims: 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. Methods: Obese animal models were induced by a high-fat diet (60% fat) for 20 weeks using the male C57BL/6 mice. 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 C-reactive protein (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.