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

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@article{bbd9dd05b02a4baca60e8dc555d57752,
title = "Heterogeneity in the perirenal region of humans suggests presence of dormant brown adipose tissue that contains brown fat precursor cells",
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.",
author = "Jespersen, {Naja Z} and Amir Feizi and Andersen, {Eline S} and Sarah Heywood and Hattel, {Helle B} and S{\o}ren Daugaard and Lone Peijs and Per Bagi and Bo Feldt-Rasmussen and Schultz, {Heidi S} and Hansen, {Ninna S} and Rikke Krogh-Madsen and Pedersen, {Bente K} and Natasa Petrovic and S{\o}ren Nielsen and Camilla Scheele",
note = "Copyright {\circledC} 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.",
year = "2019",
month = "6",
doi = "10.1016/j.molmet.2019.03.005",
language = "English",
volume = "24",
pages = "30--43",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier GmbH",

}

RIS

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

Y1 - 2019/6

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.

U2 - 10.1016/j.molmet.2019.03.005

DO - 10.1016/j.molmet.2019.03.005

M3 - Journal article

VL - 24

SP - 30

EP - 43

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

ER -

ID: 58147153