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Title:	Pten positively regulates brown adipose function, energy expenditure, and longevity
Authors:	Lopez-Guadamillas, Elena; Gómez-López, Gonzalo; Cañamero, Marta; Mulero, Francisca; González-Barroso, M. Mar ; Rial, Eduardo ; Valverde, Ángela M.; Serrano, Manuel
Keywords:	Adipose tissue Brown/metabolism DNA-Binding Proteins/genetics/metabolism Energy Metabolism/genetics/physiology Ion Channels/genetics/metabolism
Issue Date:	7-Mar-2012
Publisher:	Elsevier
Citation:	Cell Metabolism 15(3):382–394(2012)
Abstract:	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
Description:	13 páginas, 7 figuras, 7 figuras suplementarias, 7 tablas suplementarias.-- et al.
Publisher version (URL):	http://dx.doi.org/10.1016/j.cmet.2012.02.001
URI:	http://hdl.handle.net/10261/66138
DOI:	10.1016/j.cmet.2012.02.001
ISSN:	1550-4131
E-ISSN:	1932-7420
Appears in Collections:	(CIB) Artículos (IIBM) Artículos