[5] There exist several distinct subpopulations of adipose tissue macrophages that are different in terms of both origin and function.
In healthy, lean mice, nearly all macrophages are located on the outer side of blood vessels, in tight contact with adipocytes and other cells in the tissue.
It was shown that TIM4+ MHCII- macrophages originate in the embryo, even before adipocytes are fully formed, while TIM4- MHCII+ arise in the bone marrow.
[6] Macrophages from different depots (inguinal and epididymal) have recently been thoroughly characterized using single-cell RNA-sequencing in both mice and humans.
[12] Recent studies unveiled that tissue-specific resident macrophages generally cannot be classified into pure M1 or M2 polarization states.
Macrophages surrounding dying or dead adipocytes form crown-like structures (CLSs), identified by the absence of perilipin staining.
[16] Adipose tissue macrophages isolated from obese patients express growth factors, cytokines, chemokines, and proteolytic enzymes involved in the regulation of tumor growth, angiogenesis, invasion, and metastatic spread, and resemble macrophages present in tumor stroma.
Recruited macrophages are characterized by higher expression of scavenger receptors (i.e. CD36 and macrophage scavenger receptor 1 (MSR1)) and lipid-handling genes (i.e. adipose differentiation-related protein (Adfp), fatty acid-binding protein 4 (Fabp4), ApoE and ABCA1), and increased accumulation of Oil Red O-positive lipids.
[10][18] It has been shown in mice that adipose tissue macrophages regulate the age-related reduction of adipocyte lipolysis during ageing by lowering the bioavailability of noradrenaline.
[20] Tumor-associated macrophage infiltration correlates with poor prognosis in patients with breast, cervix, bladder and brain cancers.