p53 regulates expression of uncoupling protein 1 through binding and repression of PPARγ coactivator-1α
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| Název: | p53 regulates expression of uncoupling protein 1 through binding and repression of PPARγ coactivator-1α |
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| Autoři: | Philip Hallenborg, Even Fjære, Bjørn Liaset, Rasmus Koefoed Petersen, Incoronata Murano, Si Brask Sonne, Mathias Falkerslev, Sally Winther, Benjamin Anderschou Holbech Jensen, Tao Ma, Jacob B. Hansen, Saverio Cinti, Blagoy Blagoev, Lise Madsen, Karsten Kristiansen |
| Zdroj: | Hallenborg, P, Fjære, E, Liaset, B, Petersen, R K, Murano, I, Sonne, S B, Falkerslev, M, Winther, S, Jensen, B A H, Ma, T, Hansen, J B, Cinti, S, Blagoev, B, Madsen, L & Kristiansen, K 2016, ' p53 regulates expression of uncoupling protein 1 through binding and repression of PPARγ coactivator-1α ', American Journal of Physiology: Endocrinology and Metabolism, vol. 310, no. 2, pp. E116-E128 . https://doi.org/10.1152/ajpendo.00119.2015 |
| Informace o vydavateli: | American Physiological Society, 2016. |
| Rok vydání: | 2016 |
| Témata: | 0301 basic medicine, Proliferator-activated, Thermogenesis/genetics, Cells, Knockout, Adipose Tissue, White, Ion Channels/genetics, Transcription Factors/genetics, Peroxisome, Diet, High-Fat, Weight Gain, Ion Channels, Mitochondrial Proteins, Mice, 03 medical and health sciences, Adipose Tissue, Brown, Brown/metabolism, Adipocytes, Animals, Weight Gain/physiology, Cells, Cultured, Uncoupling Protein 1, Mice, Knockout, Cultured, Thermogenesis, Receptor-γ, Diet, White/metabolism, High-Fat, Adipose Tissue, Gene Expression Regulation, Adipocytes/metabolism, Mitochondrial Proteins/genetics, Tumor Suppressor Protein p53/genetics, Female, Tumor Suppressor Protein p53, Transcription Factors |
| Popis: | The tumor suppressor p53 (TRP53 in mice) is known for its involvement in carcinogenesis, but work during recent years has underscored the importance of p53 in the regulation of whole body metabolism. A general notion is that p53 is necessary for efficient oxidative metabolism. The importance of UCP1-dependent uncoupled respiration and increased oxidation of glucose and fatty acids in brown or brown-like adipocytes, termed brite or beige, in relation to energy balance and homeostasis has been highlighted recently. UCP1-dependent uncoupled respiration in classic interscapular brown adipose tissue is central to cold-induced thermogenesis, whereas brite/beige adipocytes are of special importance in relation to diet-induced thermogenesis, where the importance of UCP1 is only clearly manifested in mice kept at thermoneutrality. We challenged wild-type and TRP53-deficient mice by high-fat feeding under thermoneutral conditions. Interestingly, mice lacking TRP53 gained less weight compared with their wild-type counterparts. This was related to an increased expression of Ucp1 and other PPARGC1a and PPARGC1b target genes but not Ppargc1a or Ppargc1b in inguinal white adipose tissue of mice lacking TRP53. We show that TRP53, independently of its ability to bind DNA, inhibits the activity of PPARGC1a and PPARGC1b. Collectively, our data show that TRP53 has the ability to regulate the thermogenic capacity of adipocytes through modulation of PPARGC1 activity. |
| Druh dokumentu: | Article |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00119.2015 |
| Přístupová URL adresa: | https://www.physiology.org/doi/pdf/10.1152/ajpendo.00119.2015 https://pubmed.ncbi.nlm.nih.gov/26578713 https://ajpendo.physiology.org/content/ajpendo/310/2/E116.full.pdf https://www.physiology.org/doi/10.1152/ajpendo.00119.2015 http://findresearcher.sdu.dk/portal/files/129615967/ajpendo.00119.2015.pdf https://journals.physiology.org/doi/full/10.1152/ajpendo.00119.2015 https://pubmed.ncbi.nlm.nih.gov/26578713/ https://www.ncbi.nlm.nih.gov/pubmed/26578713 https://findresearcher.sdu.dk:8443/ws/files/129615967/ajpendo.00119.2015.pdf |
| Přístupové číslo: | edsair.doi.dedup.....b319b011243db5ae5b9630d16d940377 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | The tumor suppressor p53 (TRP53 in mice) is known for its involvement in carcinogenesis, but work during recent years has underscored the importance of p53 in the regulation of whole body metabolism. A general notion is that p53 is necessary for efficient oxidative metabolism. The importance of UCP1-dependent uncoupled respiration and increased oxidation of glucose and fatty acids in brown or brown-like adipocytes, termed brite or beige, in relation to energy balance and homeostasis has been highlighted recently. UCP1-dependent uncoupled respiration in classic interscapular brown adipose tissue is central to cold-induced thermogenesis, whereas brite/beige adipocytes are of special importance in relation to diet-induced thermogenesis, where the importance of UCP1 is only clearly manifested in mice kept at thermoneutrality. We challenged wild-type and TRP53-deficient mice by high-fat feeding under thermoneutral conditions. Interestingly, mice lacking TRP53 gained less weight compared with their wild-type counterparts. This was related to an increased expression of Ucp1 and other PPARGC1a and PPARGC1b target genes but not Ppargc1a or Ppargc1b in inguinal white adipose tissue of mice lacking TRP53. We show that TRP53, independently of its ability to bind DNA, inhibits the activity of PPARGC1a and PPARGC1b. Collectively, our data show that TRP53 has the ability to regulate the thermogenic capacity of adipocytes through modulation of PPARGC1 activity. |
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| ISSN: | 15221555 01931849 |
| DOI: | 10.1152/ajpendo.00119.2015 |