Uncoupling Protein 1 Does Not Produce Heat without Activation
Mitochondrial uncoupling protein 1 (UCP1) is the crucial mechanistic component of heat production in classical brown fat and the newly identified beige or brite fat. Thermogenesis inevitably comes at a high energetic cost and brown fat, ultimately, is an energy-wasting organ. A constrained strategy...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/5/2406 |
| _version_ | 1797475086872084480 |
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| author | Yongguo Li Tobias Fromme |
| author_facet | Yongguo Li Tobias Fromme |
| author_sort | Yongguo Li |
| collection | DOAJ |
| description | Mitochondrial uncoupling protein 1 (UCP1) is the crucial mechanistic component of heat production in classical brown fat and the newly identified beige or brite fat. Thermogenesis inevitably comes at a high energetic cost and brown fat, ultimately, is an energy-wasting organ. A constrained strategy that minimizes brown fat activity unless obligate will have been favored during natural selection to safeguard metabolic thriftiness. Accordingly, UCP1 is constitutively inhibited and is inherently not leaky without activation. It follows that increasing brown adipocyte number or UCP1 abundance genetically or pharmacologically does not lead to an automatic increase in thermogenesis or subsequent metabolic consequences in the absence of a plausible route of concomitant activation. Despite its apparent obviousness, this tenet is frequently ignored. Consequently, incorrect conclusions are often drawn from increased BAT or brite/beige depot mass, e.g., predicting or causally linking beneficial metabolic effects. Here, we highlight the inherently inactive nature of UCP1, with a particular emphasis on the molecular brakes and releases of UCP1 activation under physiological conditions. These controls of UCP1 activity represent potential targets of therapeutic interventions to unlock constraints and efficiently harness the energy-expending potential of brown fat to prevent and treat obesity and associated metabolic disorders. |
| first_indexed | 2024-03-09T20:39:11Z |
| format | Article |
| id | doaj.art-aa32e53112ff4214a02d2005b5229b70 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:39:11Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aa32e53112ff4214a02d2005b5229b702023-11-23T23:03:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235240610.3390/ijms23052406Uncoupling Protein 1 Does Not Produce Heat without ActivationYongguo Li0Tobias Fromme1Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, GermanyChair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Gregor-Mendel-Str. 2, 85354 Freising, GermanyMitochondrial uncoupling protein 1 (UCP1) is the crucial mechanistic component of heat production in classical brown fat and the newly identified beige or brite fat. Thermogenesis inevitably comes at a high energetic cost and brown fat, ultimately, is an energy-wasting organ. A constrained strategy that minimizes brown fat activity unless obligate will have been favored during natural selection to safeguard metabolic thriftiness. Accordingly, UCP1 is constitutively inhibited and is inherently not leaky without activation. It follows that increasing brown adipocyte number or UCP1 abundance genetically or pharmacologically does not lead to an automatic increase in thermogenesis or subsequent metabolic consequences in the absence of a plausible route of concomitant activation. Despite its apparent obviousness, this tenet is frequently ignored. Consequently, incorrect conclusions are often drawn from increased BAT or brite/beige depot mass, e.g., predicting or causally linking beneficial metabolic effects. Here, we highlight the inherently inactive nature of UCP1, with a particular emphasis on the molecular brakes and releases of UCP1 activation under physiological conditions. These controls of UCP1 activity represent potential targets of therapeutic interventions to unlock constraints and efficiently harness the energy-expending potential of brown fat to prevent and treat obesity and associated metabolic disorders.https://www.mdpi.com/1422-0067/23/5/2406adipocytesthermogenesisbrown fatbeige/brite cellsmolecular brakespurine nucleotides |
| spellingShingle | Yongguo Li Tobias Fromme Uncoupling Protein 1 Does Not Produce Heat without Activation International Journal of Molecular Sciences adipocytes thermogenesis brown fat beige/brite cells molecular brakes purine nucleotides |
| title | Uncoupling Protein 1 Does Not Produce Heat without Activation |
| title_full | Uncoupling Protein 1 Does Not Produce Heat without Activation |
| title_fullStr | Uncoupling Protein 1 Does Not Produce Heat without Activation |
| title_full_unstemmed | Uncoupling Protein 1 Does Not Produce Heat without Activation |
| title_short | Uncoupling Protein 1 Does Not Produce Heat without Activation |
| title_sort | uncoupling protein 1 does not produce heat without activation |
| topic | adipocytes thermogenesis brown fat beige/brite cells molecular brakes purine nucleotides |
| url | https://www.mdpi.com/1422-0067/23/5/2406 |
| work_keys_str_mv | AT yongguoli uncouplingprotein1doesnotproduceheatwithoutactivation AT tobiasfromme uncouplingprotein1doesnotproduceheatwithoutactivation |