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Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat
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SYSNO ASEP 0558033 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat Author(s) Oeckl, J. (DE)
Janovská, Petra (FGU-C) RID, ORCID
Adamcová, Kateřina (FGU-C) ORCID, RID
Bardová, Kristina (FGU-C) RID, ORCID, SAI
Brunner, S. (DE)
Dieckmann, S. (DE)
Ecker, J. (DE)
Fromme, T. (DE)
Funda, Jiří (FGU-C) ORCID
Gantert, T. (DE)
Giansanti, P. (DE)
Soledad Hidrobo, M. (DE)
Kuda, Ondřej (FGU-C) RID, ORCID, SAI
Kuster, B. (DE)
Li, Y. (DE)
Pohl, Radek (UOCHB-X) RID, ORCID
Schmitt, S. (DE)
Schweizer, S. (DE)
Zischka, H. (DE)
Zouhar, Petr (FGU-C) RID, ORCID, SAI
Kopecký, Jan (FGU-C) RID, ORCID
Klingenspor, M. (DE)Article number 101499 Source Title Molecular Metabolism. - : Elsevier - ISSN 2212-8778
Roč. 61, July (2022)Number of pages 21 s. Language eng - English Country NL - Netherlands Keywords brown adipose tissue ; UCP1-independent thermogenesis ; futile substrate cycle ; lipolysis ; re-esterification ; fatty acids OECD category Endocrinology and metabolism (including diabetes, hormones) R&D Projects GA18-04483S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support FGU-C - RVO:67985823 ; UOCHB-X - RVO:61388963 UT WOS 000804540600004 EID SCOPUS 85129587717 DOI 10.1016/j.molmet.2022.101499 Annotation Objective:Classical ATP-independent non-shivering thermogenesis enabled by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) is activated, but not essential for survival, in the cold. It has long been suspected that futile ATP-consuming substrate cycles also contribute to thermogenesis and can partially compensate for the genetic ablation of UCP1 in mouse models. Futile ATP-dependent thermogenesis could thereby enable survival in the cold even when brown fat is less abundant or missing.Methods:In this study, we explore different potential sources of UCP1-independent thermogenesis and identify a futile ATP-consuming triglyceride/fatty acid cycle as the main contributor to cellular heat production in brown adipocytes lacking UCP1. We uncover the mechanism on a molecular level and pinpoint the key enzymes involved using pharmacological and genetic interference.Results:ATGL is the most important lipase in terms of releasing fatty acids from lipid droplets, while DGAT1 accounts for the majority of fatty acid re-esterification in UCP1-ablated brown adipocytes. Furthermore, we demonstrate that chronic cold exposure causes a pronounced remodeling of adipose tissues and leads to the recruitment of lipid cycling capacity specifically in BAT of UCP1-knockout mice, possibly fueled by fatty acids from white fat. Quantification of triglyceride/fatty acid cycling clearly shows that UCP1-ablated animals significantly increase turnover rates at room temperature and below.Conclusion:Our results suggest an important role for futile lipid cycling in adaptive thermogenesis and total energy expenditure. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2023 Electronic address https://doi.org/10.1016/j.molmet.2022.101499
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