Journal
MOLECULAR METABOLISM
Volume 24, Issue -, Pages 30-43Publisher
ELSEVIER
DOI: 10.1016/j.molmet.2019.03.005
Keywords
Perirenal adipose tissue; Brown fat precursor cells; Human brown fat; Sympathetic activation; Dormant brown fat
Categories
Funding
- TrygFonden
- Danish National Research Foundation [DNRF55]
- Novo Nordisk Foundation [NNF18CC0034900]
- Lundbeck Foundation
- Danish Diabetes Academy
- Novo Nordisk Foundation
- University of Copenhagen
- Research foundation of Rigshospitalet
- Carl and Ellen Hertz Foundation
- Foundation of 1870
- Oda and Hans Svenningsens Foundation
- Foundation of the Family Hede Nielsen
- DD2 - the Danish Center for Strategic Research in Type 2 Diabetes (Danish Council for Strategic Research) [09-067009, 09-075724]
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Objective: Increasing the amounts of functionally competent brown adipose tissue (BAT) in adult humans has the potential to restore dysfunctional metabolism and counteract obesity. In this study, we aimed to characterize the human perirenal fat depot, and we hypothesized that there would be regional, within-depot differences in the adipose signature depending on local sympathetic activity. Methods: We characterized fat specimens from four different perirenal regions of adult kidney donors, through a combination of qPCR mapping, immunohistochemical staining, RNA-sequencing, and pre-adipocyte isolation. Candidate gene signatures, separated by adipocyte morphology, were recapitulated in a murine model of unilocular brown fat induced by thermoneutrality and high fat diet. Results: We identified widespread amounts of dormant brown adipose tissue throughout the perirenal depot, which was contrasted by multilocular BAT, primarily found near the adrenal gland. Dormant BAT was characterized by a unilocular morphology and a distinct gene expression profile, which partly overlapped with that of subcutaneous white adipose tissue (WAT). Brown fat precursor cells, which differentiated into functional brown adipocytes were present in the entire perirenal fat depot, regardless of state. We identified SPARC as a candidate adipokine contributing to a dormant BAT state, and CLSTN3 as a novel marker for multilocular BAT. Conclusions: We propose that perirenal adipose tissue in adult humans consists mainly of dormant BAT and provide a data set for future research on factors which can reactivate dormant BAT into active BAT, a potential strategy for combatting obesity and metabolic disease. (C) 2019 The Authors. Published by Elsevier GmbH.
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