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Augmented Adipocyte Browning and Mitochondrial Function in Periadrenal Fat but not Subcutaneous Fat in Pheochromocytoma Patients
Author(s) -
Davies Graeme Robert,
Vergnes Laurent,
Yeh Michael,
Harari Avital,
Livhits Masha,
Huang Jiaoti,
Symonds Michael,
Reue Karen,
Sacks Harold
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.307.9
Subject(s) - adipose tissue , medicine , endocrinology , adipocyte , pheochromocytoma , immunohistochemistry , chemistry , thermogenesis , biology
Background and aims This study aimed to characterize browning in periadrenal (pADR) and subcutaneous adipose tissue (SAT) depots in humans with pheochromocytoma Methods pADR and abdominal SAT samples were collected from patients undergoing adrenalectomy for aldosterone, cortisol‐secreting and non‐functioning neoplasms for the study control group (n=23) and patients with benign unilateral pheochromocytoma (n=15). Plasma catecholamine levels were measured by HPLC. The presence of unilocular or multilocular adipocytes was assessed by H&E staining and brightfield microscopy. UCP1 abundance was measured at the gene expression level by qPCR and protein by immunohistochemistry and western blotting. Mitochondria were isolated from the tissue samples and respiration analysed on an XF24 Seahorse Extracellular Flux Analyzer. Whole transcriptome analysis was carried out in pADR fat by Illumina microarray. Results 60% (9/15) of the pheo group showed browning of periadrenal fat recorded by the presence of multilocular adipocytes. Interestingly, those patients with browning in pADR fat had the highest levels of plasma catecholamines. Control pADR fat samples showed no multilocular adipocytes. No patients in either control or pheo groups showed browning of SAT. This was corroborated with UCP1 protein found in multilocular pADR fat in pheos but not in SAT. Pheo patients with multilocular pADR fat had increased mitochondrial respiration in pADR compared to controls or pheos with unilocular adipocytes. Specifically, we detected higher complex 1 to 4 respiration of the electron transport chain, while uncoupled respiration was higher. No difference was observed in respiration from SAT mitochondria. No increase was seen in plasma ANP, BNP or FGF21 in pheo patients compared to controls. Finally, microarray analysis in pADR revealed a distinct gene expression signature in pheo patients with multilocular adipocytes, characterized by enhanced expression of genes required for fatty acid oxidation and mitochondrial respiration. Conclusions Browning of pADR occurs in some patients with pheochromocytoma but is not observed in SAT. This browning may be driven by elevated plasma nor‐epinephrine in these subjects. Our data demonstrates for the first time that the multilocular pADR adipose tissue observed in pheo patients has increased mitochondrial respiration, suggesting potentially significant effects on energy metabolism in vivo. Support or Funding Information Funded by the Leducq Foundation and the Cardiometabolic Research Foundation, Los Angeles