Duration of Rapamycin Treatment Has Differential Effects on Metabolism in Mice

Anisimov, 2011, Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice, Cell Cycle, 10, 4230, 10.4161/cc.10.24.18486 Bartke, 2005, Minireview: role of the growth hormone/insulin-like growth factor system in mammalian aging, Endocrinology, 146, 3718, 10.1210/en.2005-0411 Barzilai, 2012, The critical role of metabolic pathways in aging, Diabetes, 61, 1315, 10.2337/db11-1300 Blum, 2002, Effects of sirolimus on lipids in renal allograft recipients: an analysis using the Framingham risk model, Am. J. Transplant., 2, 551, 10.1034/j.1600-6143.2002.20610.x Bonkowski, 2009, Disruption of growth hormone receptor prevents calorie restriction from improving insulin action and longevity, PLoS ONE, 4, e4567, 10.1371/journal.pone.0004567 Chang, 2009, Long-term administration of rapamycin reduces adiposity, but impairs glucose tolerance in high-fat diet-fed KK/HlJ mice, Basic Clin. Pharmacol. Toxicol., 105, 188, 10.1111/j.1742-7843.2009.00427.x Chen, 2009, mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells, Sci. Signal., 2, ra75, 10.1126/scisignal.2000559 Cunningham, 2007, mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex, Nature, 450, 736, 10.1038/nature06322 Fraenkel, 2008, mTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes, Diabetes, 57, 945, 10.2337/db07-0922 Harrison, 2009, Rapamycin fed late in life extends lifespan in genetically heterogeneous mice, Nature, 460, 392, 10.1038/nature08221 Houde, 2010, Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue, Diabetes, 59, 1338, 10.2337/db09-1324 Hughes, 2012, Cell biology. Rapamycin paradox resolved, Science, 335, 1578, 10.1126/science.1221365 Lamming, 2012, Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity, Science, 335, 1638, 10.1126/science.1215135 Li, 2010, Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis, Proc. Natl. Acad. Sci. USA, 107, 3441, 10.1073/pnas.0914798107 Matsumoto, 2006, Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism, J. Clin. Invest., 116, 2464 Pende, 2004, S6K1(-/-)/S6K2(-/-) mice exhibit perinatal lethality and rapamycin-sensitive 5′-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway, Mol. Cell. Biol., 24, 3112, 10.1128/MCB.24.8.3112-3124.2004 Polak, 2008, Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration, Cell Metab., 8, 399, 10.1016/j.cmet.2008.09.003 Prentki, 2012, Glycerolipid/free fatty acid cycle and islet β-cell function in health, obesity and diabetes, Mol. Cell. Endocrinol., 353, 88, 10.1016/j.mce.2011.11.004 Sarbassov, 2006, Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB, Mol. Cell, 22, 159, 10.1016/j.molcel.2006.03.029 Selman, 2009, Ribosomal protein S6 kinase 1 signaling regulates mammalian life span, Science, 326, 140, 10.1126/science.1177221 Sengupta, 2010, mTORC1 controls fasting-induced ketogenesis and its modulation by ageing, Nature, 468, 1100, 10.1038/nature09584 Wullschleger, 2006, TOR signaling in growth and metabolism, Cell, 124, 471, 10.1016/j.cell.2006.01.016