Lipid-associated macrophages between aggravation and alleviation of metabolic diseases.

Lipid-associated macrophages (LAMs) occur in a broad range of diseased structures and lesions in tissues important for metabolic homeostasis. LAMs can be distinguished from other tissue-resident macrophages by their lipid-handling capacity and expression of specific marker genes (e.g., Trem2 , Gpnmb , and CD36). LAMs exhibit a functional spectrum (with respect to inflammation, lipid handling, and efferocytosis) that can vary depending on metabolic and disease state, location, and microenvironmental needs. LAM pools emerge largely from monocyte-derived precursors, but may also increase in abundance through (re-)polarization and self-renewal. Evidence for the importance of LAMs in metabolic disease justifies ventures into therapeutics that manipulate LAM abundance and phenotypes. Lipid-associated macrophages (LAMs) are phagocytic cells with lipid-handling capacity identified in various metabolic derangements. During disease development, they locate to atherosclerotic plaques, adipose tissue (AT) of individuals with obesity, liver lesions in steatosis and steatohepatitis, and the intestinal lamina propria. LAMs can also emerge in the metabolically demanding microenvironment of certain tumors. In this review, we discuss major questions regarding LAM recruitment, differentiation, and self-renewal, and, ultimately, their acute and chronic functional impact on the development of metabolic diseases. Further studies need to clarify whether and under which circumstances LAMs drive disease progression or resolution and how their phenotype can be modulated to ameliorate metabolic disorders. [ABSTRACT FROM AUTHOR]