Shifts of Immune Cell Populations Differ in Response to Different Effectors of Beige Remodeling of Adipose Tissue

Highlights

• ScSeq reveals an extensive remodeling during browning of white adipose tissue

• Cold and β3Adr agonist treatment results in distinct brown/beige remodeling

• Cold induces a myeloid to lymphoid shift of the immune compartment

• β3Adr agonism leads to an interferon/Stat response and infiltration of myeloid cells

Summary

White adipose tissue (WAT) is a dynamic tissue, which responds to environmental stimuli and dietary cues by changing its morphology and metabolic capacity. The ability of WAT to undergo a beige remodeling has become an appealing strategy to combat obesity and its comorbidities. Here, by using single-cell RNA sequencing, we provide a comprehensive atlas of the cellular dynamics during beige remodeling. We reveal drastic changes both in the overall cellular composition and transcriptional states of individual cell subtypes between Adrb3- and cold-induced beiging. Moreover, we demonstrate that cold induces a myeloid to lymphoid shift of the immune compartment compared to Adrb3 activation. Further analysis showed that, Adrb3 stimulation leads to activation of the interferon/Stat1 pathways favoring infiltration of myeloid immune cells, while repression of this pathway by cold promotes lymphoid immune cell recruitment. These findings highlight that pharmacological mimetics may not provide the same beneficial effects as physiological stimuli.