Identification of metabolically activated macrophages in human adipose tissue and their possible role in preadipocyte differentiation

Abstract

Dyslipidemia can modify the function and phenotype of adipose tissue macrophages. Accumulated evidence suggests that metabolically activated (MMe) macrophages perform both detrimental and beneficial functions in adipose tissue. However, no studies evaluating their role in adipogenesis have been performed. Here, we combine in vitro assays with flow cytometry to characterize the adipose tissue macrophage populations of 32 specimens from patients with dyslipidemia and control subjects, and determine the role of MMe macrophages in the differentiation of primary human preadipocytes. We observed that the increase of MMe macrophages from adipose tissue is influenced by dyslipidemia, but the frequency of M1 and M2 macrophages did not differ when comparing both study groups. We found that MMe macrophages from dyslipidemic patients promote more adipogenic differentiation of preadipocytes compared with those from control subjects; this effect can be attributed to a mechanism governed by soluble factors and cell contact. We also observed that CD38 is expressed on CD14⁺CD80⁺CD68⁺ (M1), CD14⁺CD206⁺CD163⁺ (M2) and MMe macrophages from adipose tissue, but a higher frequency of CD38⁺ macrophages with MMe phenotype was found compared with M2. In addition, we observed a positive trend between the frequency of CD38⁺ MMe macrophages and age of dyslipidemic patients. This study demonstrates that MMe macrophages promote the differentiation of preadipocytes and this effect is favored in dyslipidemia conditions.