title: Pten positively regulates brown adipose function, energy expenditure, and longevity.
abstract: Aging in worms and flies is regulated by the PI3K/Akt/Foxo pathway. Here we extend this paradigm to mammals. Pten(tg) 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, Pten(tg) mice have an increased energy expenditure and protection from metabolic pathologies. The brown adipose tissue (BAT) of Pten(tg) 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 Pten(tg) 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.
authors.affiliation: Tumor Suppression Group, Spanish National Cancer Research Center (CNIO), Madrid E28029, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortega-Molina
authors.forename: Alejo
authors.initials: A
authors.lastname: Efeyan
authors.forename: Elena
authors.initials: E
authors.lastname: Lopez-Guadamillas
authors.forename: Maribel
authors.initials: M
authors.lastname: Muñoz-Martin
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gómez-López
authors.forename: Marta
authors.initials: M
authors.lastname: Cañamero
authors.forename: Francisca
authors.initials: F
authors.lastname: Mulero
authors.forename: Joaquin
authors.initials: J
authors.lastname: Pastor
authors.forename: Sonia
authors.initials: S
authors.lastname: Martinez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Romanos
authors.forename: M
authors.initials: M
authors.lastname: Mar Gonzalez-Barroso
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rial
authors.forename: Angela M
authors.initials: AM
authors.lastname: Valverde
authors.forename: James R
authors.initials: JR
authors.lastname: Bischoff
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002151:Calorimetry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D007093:Imidazoles / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011719:Pyrazines / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: C000604163:CNIO-PI3Ki compound; D004268:DNA-Binding Proteins; D007093:Imidazoles; D007473:Ion Channels; D024101:Mitochondrial Proteins; C521133:Prdm16 protein, mouse; D011719:Pyrazines; D014157:Transcription Factors; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D051059:PTEN Phosphohydrolase