Gene Profile of Adipose Tissue of Patients with Pheochromocytoma/Paraganglioma.

Judita Klímová,Ondřej Petrák,Matěj Zítek,Zuzana Krátká,Radka Petráková Doležalová,Květoslav Novák,Robert Holaj,Miloš Mráz,Helena Kratochvílová,Martin Haluzík,Jiří Widimský,Tomáš Zelinka,David Michalský,Zdeňka Lacinová,Veronika Todorovová,Jan Kvasnička,Denisa Haluzíková

doi:10.3390/biomedicines10030586

Judita Klímová, Ondřej Petrák + Show 15 more

Open Access

https://doi.org/10.3390/biomedicines10030586

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Abstract

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.

Highlights

Nine patients with Pheochromocytoma and functional paraganglioma (PPGL) suffered from diabetes, three of them were treated with metformin and one dose of insulin, four patients were treated only with metformin
We demonstrate in retroperitoneal visceral adipose tissue (VAT) of patients with PPGL higher expression levels of UCP1 with positive correlation to plasma norepinephrine levels and its metabolite normetanephrine and mRNA expression of ADBR3 gene encoding beta3-adrenoceptors
We demonstrate in subcutaneous adipose tissue (SAT) of PPGL higher expression of PPARGC1A and adrenoceptor beta 3 (ADRB3), together with high CIDEA levels

Summary

Introduction

Pheochromocytomas and functional paragangliomas (PPGL) are rare neuroendocrine tumors arising from chromaffin cells of adrenal medulla or extra-adrenal sympathetic creativecommons.org/licenses/by/ 4.0/). Activation of brown adipose tissue (BAT) and beige adipose tissue (BeAT) as one of the mechanisms of hypermetabolism in PPGL remains controversial. 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. 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). 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. No direct relationship with increased basal energy metabolism measured by calorimetry was found

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