Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877822000680 |
| _version_ | 1811255819907366912 |
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| author | Josef Oeckl Petra Janovska Katerina Adamcova Kristina Bardova Sarah Brunner Sebastian Dieckmann Josef Ecker Tobias Fromme Jiri Funda Thomas Gantert Piero Giansanti Maria Soledad Hidrobo Ondrej Kuda Bernhard Kuster Yongguo Li Radek Pohl Sabine Schmitt Sabine Schweizer Hans Zischka Petr Zouhar Jan Kopecky Martin Klingenspor |
| author_facet | Josef Oeckl Petra Janovska Katerina Adamcova Kristina Bardova Sarah Brunner Sebastian Dieckmann Josef Ecker Tobias Fromme Jiri Funda Thomas Gantert Piero Giansanti Maria Soledad Hidrobo Ondrej Kuda Bernhard Kuster Yongguo Li Radek Pohl Sabine Schmitt Sabine Schweizer Hans Zischka Petr Zouhar Jan Kopecky Martin Klingenspor |
| author_sort | Josef Oeckl |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T17:30:42Z |
| format | Article |
| id | doaj.art-02a486b5a3c54c2cbc43e4898dd4d342 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-04-12T17:30:42Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-02a486b5a3c54c2cbc43e4898dd4d3422022-12-22T03:23:09ZengElsevierMolecular Metabolism2212-87782022-07-0161101499Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fatJosef Oeckl0Petra Janovska1Katerina Adamcova2Kristina Bardova3Sarah Brunner4Sebastian Dieckmann5Josef Ecker6Tobias Fromme7Jiri Funda8Thomas Gantert9Piero Giansanti10Maria Soledad Hidrobo11Ondrej Kuda12Bernhard Kuster13Yongguo Li14Radek Pohl15Sabine Schmitt16Sabine Schweizer17Hans Zischka18Petr Zouhar19Jan Kopecky20Martin Klingenspor21Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL Institute for Food & Health, Technical University of Munich, Freising, GermanyLaboratory of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Czech RepublicLaboratory of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Czech RepublicLaboratory of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Czech RepublicChair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL Institute for Food & Health, Technical University of Munich, Freising, GermanyChair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL Institute for Food & Health, Technical University of Munich, Freising, GermanyZIEL Institute for Food & Health, Technical University of Munich, Freising, GermanyChair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL Institute for Food & Health, Technical University of Munich, Freising, GermanyLaboratory of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Czech RepublicChair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL Institute for Food & Health, Technical University of Munich, Freising, GermanyChair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; Bavarian Center for Biomolecular Mass Spectrometry, Technical University of Munich, Freising, GermanyChair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL Institute for Food & Health, Technical University of Munich, Freising, GermanyLaboratory of Metabolism of Bioactive Lipids, Institute of Physiology of the Czech Academy of Sciences, Czech RepublicChair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; Bavarian Center for Biomolecular Mass Spectrometry, Technical University of Munich, Freising, GermanyChair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL Institute for Food & Health, Technical University of Munich, Freising, GermanyNMR spectroscopy, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Czech RepublicInstitute of Toxicology and Environmental Hygiene, School of Medicine, Technical University of Munich, Munich, GermanyChair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL Institute for Food & Health, Technical University of Munich, Freising, GermanyInstitute of Toxicology and Environmental Hygiene, School of Medicine, Technical University of Munich, Munich, Germany; Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, Munich, GermanyLaboratory of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Czech RepublicLaboratory of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Czech Republic; Corresponding author. Laboratory of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic.Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany; EKFZ - Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany; ZIEL Institute for Food & Health, Technical University of Munich, Freising, Germany; Corresponding author. Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany.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.http://www.sciencedirect.com/science/article/pii/S2212877822000680Brown adipose tissueUCP1-independent thermogenesisFutile substrate cycleLipolysisRe-esterificationFatty acids |
| spellingShingle | Josef Oeckl Petra Janovska Katerina Adamcova Kristina Bardova Sarah Brunner Sebastian Dieckmann Josef Ecker Tobias Fromme Jiri Funda Thomas Gantert Piero Giansanti Maria Soledad Hidrobo Ondrej Kuda Bernhard Kuster Yongguo Li Radek Pohl Sabine Schmitt Sabine Schweizer Hans Zischka Petr Zouhar Jan Kopecky Martin Klingenspor Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat Molecular Metabolism Brown adipose tissue UCP1-independent thermogenesis Futile substrate cycle Lipolysis Re-esterification Fatty acids |
| title | Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat |
| title_full | Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat |
| title_fullStr | Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat |
| title_full_unstemmed | Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat |
| title_short | Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat |
| title_sort | loss of ucp1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat |
| topic | Brown adipose tissue UCP1-independent thermogenesis Futile substrate cycle Lipolysis Re-esterification Fatty acids |
| url | http://www.sciencedirect.com/science/article/pii/S2212877822000680 |
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