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Sci. Signal., 17 March 2009 RESEARCHObesity Increases Vascular Senescence and Susceptibility to Ischemic Injury Through Chronic Activation of Akt and mTORChao-Yung Wang1, Hyung-Hwan Kim1, Yukio Hiroi1, Naoki Sawada1, Salvatore Salomone2, Laura E. Benjamin3, Kenneth Walsh4, Michael A. Moskowitz2, and James K. Liao1*
1 Vascular Medicine Research Unit, Brigham and Womens Hospital and Harvard Medical School, Cambridge, MA 02139, USA. Abstract: Obesity and age are important risk factors for cardiovascular disease. However, the signaling mechanism linking obesity with age-related vascular senescence is unknown. Here we show that mice fed a high-fat diet show increased vascular senescence and vascular dysfunction compared to mice fed standard chow and are more prone to peripheral and cerebral ischemia. All of these changes involve long-term activation of the protein kinase Akt. In contrast, mice with diet-induced obesity that lack Akt1 are resistant to vascular senescence. Rapamycin treatment of diet-induced obese mice or of transgenic mice with long-term activation of endothelial Akt inhibits activation of mammalian target of rapamycin (mTOR)–rictor complex 2 and Akt, prevents vascular senescence without altering body weight, and reduces the severity of limb necrosis and ischemic stroke. These findings indicate that long-term activation of Akt-mTOR signaling links diet-induced obesity with vascular senescence and cardiovascular disease. * To whom correspondence should be addressed. E-mail: jliao{at}rics.bwh.harvard.edu
Citation: C.-Y. Wang, H.-H. Kim, Y. Hiroi, N. Sawada, S. Salomone, L. E. Benjamin, K. Walsh, M. A. Moskowitz, J. K. Liao, Obesity Increases Vascular Senescence and Susceptibility to Ischemic Injury Through Chronic Activation of Akt and mTOR. Sci. Signal. 2, ra11 (2009). The editors suggest the following Related Resources on Science sites:In Science Signaling
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Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882