Adipose Tissue Functions as a Humoral-Neuronal Hub Coordinating Systemic Energy Balance and Cardiometabolic Health

The global prevalence of obesity and type 2 diabetes mellitus (T2DM) underscores a critical public health crisis, often stemming from dysregulated energy homeostasis. Current therapeutic strategies primarily focus on caloric restriction, but their long-term efficacy is limited by compensatory metabolic adaptations. Adipose tissue, traditionally viewed as an energy storage depot, has emerged as a dynamic endocrine organ with a far more complex role in systemic metabolic regulation and cardiometabolic health. Understanding its intricate communication networks is crucial for developing novel, more effective interventions.

This review synthesizes current understanding of adipose tissue's multifaceted role in metabolic regulation. It examines both humoral signals, including peptide hormones, lipid mediators, metabolites, chemokines, and exosomal microRNAs, and neuronal circuits involving sympathetic efferents and sensory afferents. The authors also discuss how nutritional, environmental (e.g., cold exposure, exercise), and pathological states (e.g., obesity, T2DM, lipodystrophy, ageing-associated disorders) dynamically modulate these endocrine and neural outputs. Methodological innovations like omics based on mass spectrometry or liquid chromatography-mass spectrometry, secretome labelling, adipose tissue organoid models, and click chemistry are highlighted for their role in high-resolution characterization.

Adipose tissue coordinates systemic energy balance and cardiometabolic health through a dual system of humoral signals and precise neuronal circuits. Humoral signals encompass a diverse array of molecules, including peptide hormones, lipid mediators, metabolites, chemokines, and exosomal microRNAs, all secreted by various adipose depots. These signals exert systemic effects on distant organs. Neuronal circuits provide rapid and precise control over adipose function. Sympathetic efferents are shown to trigger lipolysis in white adipose tissue (WAT) and thermogenesis in brown adipose tissue (BAT). Conversely, sensory afferents detect chemical, thermal, and mechanical signals, subsequently adjusting sympathetic activity to maintain homeostasis. Nutritional and environmental stimuli, such as diet, cold exposure, and exercise, along with pathological states like obesity and T2DM, dynamically modulate these complex endocrine and neural outputs. The review emphasizes that advanced methodologies, including omics and adipose tissue organoid models, are enabling a deeper characterization of these adipose-derived signals and their targets. > Adipose tissue coordinates systemic energy balance and cardiometabolic health through a dual system of humoral signals (peptide hormones, lipid mediators, microRNAs) and precise neuronal circuits (sympathetic efferents, sensory afferents).