Unravel the ontogeny and function of adipose tissue macrophage subpopulations in health and obesity

Immune cell infiltration in visceral adipose tissue (VAT) during obesity is associated with local chronic inflammation and the development of metabolic syndromes, such as insulin resistance and type 2 diabetes. Among the infiltrating immune cells, adipose tissue macrophages (ATMs) are the most abundant leukocyte fractions, they are not only the key cells for maintenance of VAT homeostasis, but also the major players in controlling metabolic dysregulation during aging and obesity. It is well established that functional distinct ATM subsets exist in VAT, but their specific functional contribution during health and obesity still need to be clarified. In my project, three phenotypically distinct subpopulations of F4/80hi ATMs (MHCIIlow, MHCII+ CD11c- and MHCII+CD11c+) showing different frequencies, morphology, transcriptomic profiles and lipid content during the progression of obesity are present in VAT. Each of the ATM subset displays characteristic half-lives and turnover rates to ensure their presence in the V A T during obesity-mediated tissue remodeling. The long-lived MHCIIlow A TMs maintain their embryonic origin even during obesity, while the other two ATM subsets are rapidly replenished by bone marrow-derived infiltrating monocytes upon high-fat feeding. Furthermore, our functional studies show that MHCII+CD11c+ ATM subset, which is almost absent in normal lean tissue but is massively expanded in the VAT during obesity, not only contains adipocyte hypertrophy and dysfunction, but is also important for lipid buffering, suggesting that it is crucial in regulating adipose tissue function in obesity. Therefore, we provide additional evidence for beneficial functions of macrophages in obesity-induced adipose tissue remodeling.Doctor of Philosoph