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Mol Metab. 2019 Jun;24:30-43. doi: 10.1016/j.molmet.2019.03.005. Epub 2019 Mar 15.

Heterogeneity in the perirenal region of humans suggests presence of dormant brown adipose tissue that contains brown fat precursor cells.

Author information

1
The Centre of Inflammation and Metabolism and Centre for Physical Activity Research Rigshospitalet, University Hospital of Copenhagen, 2100, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Danish PhD School of Molecular Metabolism, Odense, Denmark.
2
Novo Nordisk Research Center Oxford, Denmark.
3
The Centre of Inflammation and Metabolism and Centre for Physical Activity Research Rigshospitalet, University Hospital of Copenhagen, 2100, Denmark.
4
Department of Pathology, Rigshospitalet, Denmark.
5
The Centre of Inflammation and Metabolism and Centre for Physical Activity Research Rigshospitalet, University Hospital of Copenhagen, 2100, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
6
Department of Urology, Rigshospitalet, Denmark.
7
Department of Nephrology, Rigshospitalet, Denmark.
8
Novo Nordisk A/S, Måløv, Denmark.
9
Danish PhD School of Molecular Metabolism, Odense, Denmark; Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Denmark.
10
The Centre of Inflammation and Metabolism and Centre for Physical Activity Research Rigshospitalet, University Hospital of Copenhagen, 2100, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
11
Department of Molecular Biosciences, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, 106 91, Stockholm, Sweden.
12
The Centre of Inflammation and Metabolism and Centre for Physical Activity Research Rigshospitalet, University Hospital of Copenhagen, 2100, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: cs@sund.ku.dk.

Abstract

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.

KEYWORDS:

Brown fat precursor cells; Dormant brown fat; Human brown fat; Perirenal adipose tissue; Sympathetic activation

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