Background: Brown adipose tissue (BAT) is a therapeutic target to combat obesity and related disorders. Pheochromocytoma and functional paraganglioma (PPGL) are associated with activated BAT due to catecholamine excess. Our aim was to evaluate BAT activity by gene profile and assess its relation to clinical characteristics and overproduced catecholamine. Methods: mRNA expression of 15 genes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was measured via RT-PCR in 25 patients with PPGL and 14 controls undergoing cholecystectomy. Results: We found in VAT of PPGL higher expression of UCP1 (p < 0.001), CEBPB, PPARGC1A (both p < 0.001), PRDM16 (p = 0.069) and DIO2 (p = 0.005). UCP1 expression correlated only with norepinephrine levels and its metabolite. UCP1 expression, among others, correlated negatively with BMI, age and positively with HDLc levels. Dominance of BAT or BeAT markers was not assessed in PPGL. In SAT of PPGL, we found higher expression of ADRB3, CIDEA (both p < 0.05), and PPARGC1A (p = 0.001), but not UCP1. Conclusion: We demonstrate signs of UCP1-dependent norepinephrine-induced thermogenesis connected with higher expression of DIO2, PPARGC1A, CEBPB and PRDM16 in retroperitoneal VAT of PPGL and its relations to circulating HDLc and triglycerides levels. However, no direct relationship with increased basal energy metabolism measured by calorimetry was found.

1st Department of Surgery 1st Faculty of Medicine and General Faculty Hospital Charles University 128 00 Prague Czech Republic

Center for Experimental Medicine and Diabetes Center Institute for Clinical and Experimental Medicine 140 00 Prague Czech Republic

Center of Hypertension 3rd Department of Medicine 1st Faculty of Medicine and General Faculty Hospital Charles University 128 00 Prague Czech Republic

Department of Urology 1st Faculty of Medicine and General Faculty Hospital Charles University 128 00 Prague Czech Republic

Institute for Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine and General Faculty Hospital Charles University 128 00 Prague Czech Republic

Institute of Sport Medicine 1st Faculty of Medicine and General Faculty Hospital Charles University 128 00 Prague Czech Republic

Laboratory of Endocrinology and Metabolism 3rd Department of Medicine 1st Faculty of Medicine and General Faculty Hospital Charles University 128 00 Prague Czech Republic

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Hypermetabolism and Substrate Utilization Rates in Pheochromocytoma and Functional Paraganglioma