Adipose tissue as a humoral–neuronal hub in metabolic regulation

Abstract

Adipose tissue has emerged as a dynamic endocrine organ that coordinates systemic energy balance and cardiometabolic health. This Review highlights the dual humoral and neuronal pathways through which adipose tissue regulates systemic metabolism. Humoral signals include peptide hormones, lipid mediators, metabolites, chemokines and exosomal microRNAs secreted by adipose depots. Neuronal circuits control adipose function rapidly and precisely: sympathetic efferents trigger lipolysis in white adipose tissue and thermogenesis in brown adipose tissue, whereas sensory afferents detect chemical, thermal and mechanical signals to adjust sympathetic activity. Nutritional and environmental stimuli (for example, diet, cold exposure and exercise), along with pathological states (for example, obesity, type 2 diabetes mellitus, lipodystrophy and ageing-associated disorders), dynamically modulate these endocrine and neural outputs. Methodological innovations, such as omics based on mass spectrometry or liquid chromatography–mass spectrometry, secretome labelling, adipose tissue organoid models and click chemistry, enable high-resolution characterization of adipose-derived signals and their targets. Finally, we discuss translational opportunities, including synthetic analogues of lipophilic hormones, and future therapeutic strategies that harness adipose communication networks. This Review highlights adipose humoral and neuronal pathways that operate through inter-organ communication to regulate systemic metabolism, examines how physiological and pathological contexts shape these signals, and explores emerging technologies and translational opportunities for targeting adipose networks in metabolic disease.