Postdoctoral associate Ragon Institute of MGH, MIT, and Harvard Cambridge, Massachusetts, United States
Introduction/Rationale: Metabolic balance within adipose tissue is tightly controlled by both the peripheral nervous system and the local immune environment. Recent studies highlighted an underappreciated interplay between adipose-innervating peripheral nerves and immune cells, especially the resident tissue macrophages that contribute to proper energy expenditure and metabolic health. However, the mechanistic basis of this bidirectional neuro–macrophage communication in regulating WAT metabolic homeostasis remains largely unknown.
Methods: To test whether perivascular macrophage reprogramming changes sympathetic innervation, we will quantify sympathetic fiber density/structure in WAT by immunostaining and confocal imaging and assess sympathetic activity by measuring norepinephrine and catecholamine-pathway markers in adipose tissue. To identify macrophage-derived mechanisms, we will transcriptomically profile perivascular macrophages from reprogrammed and control mice, prioritizing secreted/extracellular programs linked to axon outgrowth and guidance. Top candidates will be functionally tested using sympathetic neuron neurite-outgrowth assays and complementary in vivo perturbation approaches. Finally, we will evaluate metabolic impact by measuring thermogenic/lipolytic gene programs and systemic phenotypes.
Results: Transcriptional reprogramming of adipose perivascular macrophages is associated with higher sympathetic fiber density in white adipose tissue. This remodeling correlates with improved metabolic outcomes, including protection from early-onset diet-induced obesity.
Conclusion: These findings support a model in which resident perivascular macrophages actively modulate sympathetic remodeling in adipose tissue to promote metabolic homeostasis.
