From endocrine to immune: therapeutic potential of brown adipose tissue in remodelling the cardiovascular immune microenvironment

Abstract

Brown adipose tissue (BAT) has transcended its classical role as an energy-dissipating thermogenic organ, emerging as a pivotal endocrine and immunoregulatory hub. This review systematically delineates the novel BAT endocrine mediator-cardiovascular immune microenvironment axis. We elucidate how BAT-derived secretomes, encompassing specific batokines, lipid mediators and extracellular vesicles(EVs), orchestrate profound cross-organ crosstalk to modulate systemic cardiovascular immunity. Pathophysiological stress, including obesity and ageing, precipitates BAT whitening and dysregulates local neuro-immune-metabolic reflex arcs, thereby exacerbating atherosclerosis(AS), hypertension and heart failure. Crucially, the phenotypic transformation of perivascular adipose tissue(PVAT) is intimately linked to localized vascular inflammation and macrophage polarization. Furthermore, we critically evaluate cutting-edge pharmacological interventions targeting key pathways, including FGF21 signaling, BAT-derived exosomes, and specific lipid mediators. These therapeutic modalities span conventional adrenergic activators, advanced nanotechnological delivery systems and cell-free epigenetic therapies. By circumventing the cardiovascular toxicities of systemic sympathetic overactivation, these targeted strategies precisely remodel the adipose microenvironment. Ultimately, harnessing the profound immunometabolic plasticity of BAT unveils a groundbreaking therapeutic paradigm for combatting advanced cardiometabolic diseases.