Endocrine Abstracts

Pheochromocytomas are catecholamine-producing tumours with diverse cardiovascular and metabolic outcomes including insulin resistance and weight loss. However, impacts on adjacent and distal fat depots are not fully defined and more particularly concerning induction of beige/brown adipose tissue (AT). The aim of the study is to characterize the cellular composition, the metabolic function and the expression of brown AT markers in matched perirenal (PRAT) and abdominal subcutaneous AT (SAT) in association or not with pheochromocytoma. Paired biopsies from PRAT and SAT are collected from patients undergoing adrenalectomy for pheochromocytoma, cortisol-producing adrenal adenoma or non-secreting and benign adrenal tumours. AT are enzymatically digested to isolate mature adipocytes and stroma-vascular fraction (SVF) cells. The adipocyte diameter repartition is determined by image analysis, lipolytic activity by glycerol and free fatty acid quantifications in the presence of lipolytic pharmacological agents (isoprenaline, epinephrine, atrial natriuretic peptide ANP), and finally adipocyte gene expression is analysed by RT-qPCR approaches. The cellular composition of the SVF (progenitor, endothelial and immune cells) is determined by flow cytometry analyses. Our results demonstrate that, whatever the clinical context, PRAT adipocytes are less hypertrophied than paired SAT adipocytes, and that pheochromocytoma patients tend to exhibit smaller adipocytes whatever the AT depot. Multilocular brown-like adipocytes are observed in PRAT only and in patients with pheochromocytoma. Their presence is associated with higher beige/brown gene expression marker (UCP1, uncoupling protein 1). PRAT and SAT adipocytes show distinct lipolytic responses to beta-adrenergic receptor agonist (isoprenaline, epinephrine) and ANP in pheochromocytoma patients compared to others. In agreement, the transcriptomic profiles of adrenergic receptors, lipolytic enzymes and lipid droplet associated proteins are different according to AT depot. Finally, the distribution of progenitor cell subsets, macrophages and lymphocytes, specific of PRAT and SAT, is modulated in pheochomocytoma patients. Our study shows that PRAT exhibits specific cellularity and metabolic lipolytic function compared to SAT and both AT depots are different in pheochromocytoma patients. Finally, presence of brown-like multilocular and UCP1 positive adipocytes is only observed in PRAT from such patients.