SMOOTH MUSCLE CELL DERIVED CXCL12 DIRECTS MACROPHAGE ACCRUAL AND SYMPATHETIC INNERVATION TO CONTROL THERMOGENIC ADIPOSE TISSUE
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Brown adipose tissue (BAT) adaptive thermogenesis is regulated by sympathetic innervation. However, the cellular and molecular processes that control these mechanisms are not yet fully understood. In our study, we find that the elimination of smooth muscle cells (SMCs) within BAT caused BAT to shrink, with demonstrated lipid accumulation, reduced thermogenic response, and decreased sympathetic innervation. We discovered that SMCs control the presence of the CXCL motif chemokine ligand 12 (CXCL12), driving M2-macrophages accrual and reinforcing sympathetic nerve activity. Deletion of CXCL12 in SMCs results in increased BAT lipids, lower energy expenditure, and greater vulnerability to diet-induced metabolic problems. Conversely, administering recombinant CXCL12 to high fat diet or ob/ob mice was sufficient to enhance M2-macrophage presence and encourage sympathetic innervation, reviving BAT's morphology and its thermogenic capability.