Adrenal - adipose tissue crosstalk in health and disease

Abstract Adipose tissue closely interacts with the adrenal glands to regulate metabolism, energy balance and stress responses. While the adrenal cortex secretes glucocorticoids and mineralocorticoids that influence adipose tissue distribution, lipid storage, and browning, the adrenal medulla releases catecholamines that acutely activate thermogenesis in brown and beige adipocytes. Under physiological conditions, this bidirectional crosstalk maintains energy homeostasis and cardiovascular stability. However, in adrenal diseases such as Cushing syndrome, primary aldosteronism, adrenocortical carcinoma or pheochromocytoma, excess hormone secretion disrupts this balance, leading to adipose tissue dysfunction, altered adipokine secretion, and adverse metabolic profiles, including insulin resistance, visceral adiposity, and hypertension. Emerging evidence suggests that peri-adrenal adipose tissue may modulate adrenal tumor biology through endocrine and paracrine signals, and immune cell infiltration, with potential effects on disease progression and clinical presentation. Uncovering cellular and molecular mechanisms underlying the crosstalk between adrenal gland and adipose tissue may reveal new therapeutic targets for reduction of cardiometabolic complications in patients with adrenal disorders. Here, we discuss how two endocrine organs - adrenal gland and adipose tissue - interact with each other under physiological and pathophysiological conditions and examine whether these interactions influence the progression of adrenal tumors and how this affects systemic metabolic health.