TY - JOUR
T1 - Heterogeneity in the perirenal region of humans suggests presence of dormant brown adipose tissue that contains brown fat precursor cells
AU - Jespersen, Naja Z
AU - Feizi, Amir
AU - Andersen, Eline S
AU - Heywood, Sarah
AU - Hattel, Helle B
AU - Daugaard, Søren
AU - Peijs, Lone
AU - Bagi, Per
AU - Feldt-Rasmussen, Bo
AU - Schultz, Heidi S
AU - Hansen, Ninna S
AU - Krogh-Madsen, Rikke
AU - Pedersen, Bente K
AU - Petrovic, Natasa
AU - Nielsen, Søren
AU - Scheele, Camilla
N1 - Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
KW - Brown fat precursor cells
KW - Dormant brown fat
KW - Human brown fat
KW - Perirenal adipose tissue
KW - Sympathetic activation
U2 - 10.1016/j.molmet.2019.03.005
DO - 10.1016/j.molmet.2019.03.005
M3 - Journal article
C2 - 31079959
VL - 24
SP - 30
EP - 43
JO - Molecular Metabolism
JF - Molecular Metabolism
SN - 2212-8778
ER -