Pten Positively Regulates Brown Adipose Function, Energy Expenditure, and Longevity

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• 作者：Ana Ortega-Molina¹ ; Alejo Efeyan¹ ; Elena Lopez-Guadamillas¹ ; Maribel Muñ ; oz-Martin¹ ; Gonzalo Gó ; mez-Ló ; pez² ; Marta Cañ ; amero³ ; Francisca Mulero⁴ ; Joaquin Pastor⁵ ; Sonia Martinez⁵ ; Eduardo Romanos⁶ ; M. Mar  ; Gonzalez-Barroso⁷ ; Eduardo Rial⁷ ; Angela  ; M. Valverde⁸ ; ⁹ ; James  ; R. Bischoff⁵ ; Manuel Serrano¹ ; ^{mserrano@cnio.es}
• 刊名：Cell Metabolism
• 出版年：2012
• 出版时间：7 March, 2012
• 年：2012
• 卷：15
• 期：3
• 页码：382-394
• 全文大小：1775 K

文摘

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Summary

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 Cebp¦Â 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.