Human Adipose Tissue Macrophages: M1 and M2 Cell Surface Markers in Subcutaneous and Omental Depots and after Weight Loss

Abstract

Context: Macrophages accumulate in adipose tissue and possibly participate in metabolic complications in obesity. Macrophage number varies with adipose tissue site and weight loss, but whether this is accompanied by phenotypic changes is unknown. Objective: The objective of the study was to characterize the activation state of adipose tissue macrophages in human obesity. Design/Setting: We performed a single-center prospective study. Participants/Interventions: Paired biopsies of sc and omental adipose tissue were obtained during gastric surgery in 16 premenopausal obese women (aged 41.1 ± 8.6 yr; body mass index 43.8 ± 3.4 kg/m2). Subcutaneous adipose tissue biopsies were obtained 3 months later in obese subjects and in 10 nonobese women (aged 43.3 ± 3.5 yr; body mass index 22.5 ± 0.75 kg/m2). The number of macrophages stained with CD40, CD206, and CD163 surface markers was determined by immunochemistry. Main Outcomes: The number of CD40+ macrophages significantly increased with obesity and in omental vs. sc adipose tissue in obese women. No significant changes in CD163+ and CD206+ macrophage counts was found with obesity and fat pad anatomical location. Three months after gastric surgery, the ratio of CD40+ to CD206+ macrophages was 2-fold lower than before surgery in the sc adipose tissue of obese subjects (P < 0.001) due to a concomitant decrease of CD40+ and increase of CD206+ macrophages counts. Conclusion: We suggest that the activation state of adipose tissue macrophages is weighted toward M1 over M2 status in obese subjects and switch to a less proinflammatory profile 3 months after gastric bypass. Immunohistochemistry analyses suggest that gastric surgery switches the activation state of adipose tissue macrophages towards a M2-oriented, less pro-inflammatory phenotype in morbidly obese subjects.