Investigation of the role of CD300e in regulating lipid homeostasis in obese adipose tissue

Obesity is a major global health concern, closely associated with chronic low-grade inflammation and systemic metabolic dysfunction. Among the key immune cells involved, adipose tissue macrophages (ATMs) are critical for maintaining adipose tissue homeostasis by acting as lipid sensors and mediators of tissue remodeling. Recent findings from our laboratory have identified CD300e, an immune receptor selectively expressed by myeloid cells, as a novel modulator of ATM function. In a CD300e knock-out (KO) mouse model fed a high-fat diet (HFD), the absence of this receptor resulted in significant adipocyte hypertrophy and reduced insulin sensitivity. Notably, macrophages isolated from the visceral adipose tissue (VAT) of KO mice showed increased expression of genes associated with lipid-associated macrophages (LAMs) compared to wild-type (WT) counterparts, suggesting a role for CD300e in limiting lipid overload and preventing metabolic imbalance. The aim of this thesis was to reproduce these in vivo observations in vitro, in order to investigate the molecular mechanisms underlying the phenotype observed in CD300e-deficient animals. The study has been focused on two main objectives: assessing lipid uptake by KO macrophages and identifying factors driving adipocyte hypertrophy. To this end, multiple co-culture systems were established using VAT and monocytes isolated from bone marrow.