Pten Positively Regulates Brown Adipose Function, Energy Expenditure, and Longevity
| Autor: | Gonzalo Gómez-López, Ángela M. Valverde, Alejo Efeyan, M. Mar González-Barroso, Elena Lopez-Guadamillas, Eduardo Rial, Sonia Martinez, Joaquín Pastor, Marta Cañamero, Ana Ortega-Molina, James R. Bischoff, Maribel Muñoz-Martin, Manuel Serrano, Eduardo Romanos, Francisca Mulero |
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| Přispěvatelé: | Comunidad de Madrid, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III |
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Physiology Longevity Adipose tissue Mice Transgenic Biology Calorimetry Ion Channels Mitochondrial Proteins Mice Adipose Tissue Brown Internal medicine Brown/metabolism Brown adipose tissue medicine Uncoupling protein PTEN Animals Energy Metabolism/genetics/physiology Protein kinase B Molecular Biology PI3K/AKT/mTOR pathway Uncoupling Protein 1 PRDM16 Imidazoles PTEN Phosphohydrolase Cell Biology Thermogenin DNA-Binding Proteins medicine.anatomical_structure Endocrinology DNA-Binding Proteins/genetics/metabolism Pyrazines biology.protein Energy Metabolism Ion Channels/genetics/metabolism Transcription Factors |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1550-4131 2009-0811 |
| DOI: | 10.1016/j.cmet.2012.02.001 |
| Popis: | 13 páginas, 7 figuras, 7 figuras suplementarias, 7 tablas suplementarias.-- et al. Aging in worms and flies is regulated by the PI3K/Akt/Foxo pathway. Here we extend this paradigm to mammals. Ptentg mice carrying additional genomic copies of Pten are protected from cancer and present a significant extension of life span that is independent of their lower cancer incidence. Interestingly, Ptentg mice have an increased energy expenditure and protection from metabolic pathologies. The brown adipose tissue (BAT) of Ptentg mice is hyperactive and presents high levels of the uncoupling protein Ucp1, which we show is a target of Foxo1. Importantly, a synthetic PI3K inhibitor also increases energy expenditure and hyperactivates the BAT in mice. These effects can be recapitulated in isolated brown adipocytes and, moreover, implants of Ptentg fibroblasts programmed with Prdm16 and Cebpβ form subcutaneous brown adipose pads more efficiently than wild-type fibroblasts. These observations uncover a role of Pten in promoting energy expenditure, thus decreasing nutrient storage and its associated damage Work in the laboratory of A.M.V. was funded by grant SAF2009-08114 and by the CIBERDEM (ISCIII), and work in the laboratory of E. Rial was funded by grants SAF2010-20256 and Consolider-Ingenio CSD2007-00020. A.O.-M. was recipient of a predoctoral contract of the Regional Government of Madrid. E.L.-G. was recipient of a predoctoral contract from the Spanish Ministry of Education. M.M.G.-B. was supported by the “Ramon y Cajal” program of the Spanish Ministry of Science and Innovation. |
| Databáze: | OpenAIRE |
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