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Vergnes, Laurent and Davies, Graeme R. and Lin, Jason Y. and Yeh, Michael W. and Livhits, Masha J. and Harari, Avital and Symonds, Michael E. and Sacks, Harold S. and Reue, Karen (2016) Adipocyte browning and higher mitochondrial function in peri-adrenal but not subcutaneous fat in pheochromocytoma. Journal of Clinical Endocrinology and Metabolism, 101 (11). pp. 4440-4448. ISSN 1945-7197

Abstract

Context:

Patients with pheochromocytoma (pheo) show presence of multilocular adipocytes that express uncoupling protein (UCP) 1 within periadrenal (pADR) and omental (OME) fat depots. It has been hypothesized that this is due to adrenergic stimulation by catecholamines produced by the pheo tumors.

Objective:

To characterize the prevalence and respiratory activity of brown-like adipocytes within pADR, OME and subcutaneous (SC) fat depots in human adult pheo patients.

Design:

This was an observational cohort study.

Setting:

University hospital.

Patients:

We studied 46 patients who underwent surgery for benign adrenal tumors (21pheos and 25 controls with adrenocortical adenomas).

Main outcome measure:

We characterized adipocyte browning in pADR, SC, and OME fat depots for histological and immunohistological features, mitochondrial respiration rate, and gene expression. We also determined circulating levels of catecholamines and other browning-related hormones.

Results:

11 of 21 pheo pADR adipose samples, but only 1 of 25 pADR samples from control patients, exhibited multilocular adipocytes. The pADR browning phenotype was associated with higher plasma catecholamines and raised UCP1. Mitochondria from multilocular pADR fat of pheo patients exhibited increased rates of coupled and uncoupled respiration. Global gene expression analysis in pADR fat revealed enrichment in β-oxidation genes in pheo patients with multilocular adipocytes. No SC or OME fat depots exhibited aspects of browning.

Conclusion:

Browning of the pADR depot occurred in half of pheo patients and was associated with increased catecholamines and mitochondrial activity. No browning was detected in other fat depots, suggesting that other factors are required to promote browning in these depots.

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