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Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging
Published on: July 1, 2021
Adipocyte Browning and Higher Mitochondrial Function in Periadrenal But Not SC Fat in Pheochromocytoma
Laurent Vergnes1, Graeme R Davies1, Jason Y Lin1
1Department of Human Genetics (L.V., J.Y.L., K.R.), David Geffen School of Medicine at UCLA, Los Angeles, California; Academic Division of Child Health, Obstetrics and Gynaecology (G.R.D., M.E.S.), School of Medicine, Queen's Medical Centre, The University of Nottingham, Nottingham, United Kingdom; Section of Endocrine Surgery (M.W.Y., M.J.L., A.H.), David Geffen School of Medicine at UCLA, Los Angeles, California; Endocrinology and Diabetes Division (H.S.S.), VA Greater Los Angeles Healthcare System, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; Molecular Biology Institute (K.R.), University of California, Los Angeles, Los Angeles, California.
Context:
Patients with pheochromocytoma (pheo) show presence of multilocular adipocytes that express uncoupling protein 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 SC fat depots in human adult pheo patients.
Design:
This was an observational cohort study.
Setting:
The study took place in a university hospital.
Patients:
We studied 46 patients who underwent surgery for benign adrenal tumors (21 pheos 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:
Eleven of 21 pheo pADR adipose samples, but only one of 25 pADR samples from control patients exhibited multilocular adipocytes. The pADR browning phenotype was associated with higher plasma catecholamines and raised uncoupling protein 1. 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.
