Unveiling the impact of TREM-2⁺ Macrophages in metabolic disorders

The Triggering Receptor Expressed on Myeloid cells 2 (TREM-2) has been widely known by its anti-inflammatory activity. It can be activated in response to microbes and tissue damage, leading to phagocytosis, autophagy, cell polarization and migration, counter inflammation, and tissue repair. So far, the receptor has been largely explored in neurodegenerative disorders, however, a growing number of studies have been investigating its contribution in different pathological conditions, including metabolic diseases, in which (resident) macrophages play a crucial role. In this regard, TREM-2 + macrophages have been implicated in the onset and development of obesity, atherosclerosis, and fibrotic liver disease. These macrophages can be detected in the brain, white adipose tissue, liver, and vascular endothelium. In this review we discuss how different murine models have been demonstrating the ability of such cells to contribute to tissue and body homeostasis by phagocytosing cellular debris and lipid structures, besides contributing to lipid homeostasis in metabolic diseases. Therefore, understanding the role of TREM-2 in metabolic disorders is crucial to expand our current knowledge concerning their immunopathology as well as to foster the development of more targeted therapies to treat such conditions.