Rapamycin and Dietary Restriction Induce MetabolicallyDistinctive Changes in Mouse Liver

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  • Dietary restriction (DR) is the gold standard intervention used to delay aging, and much recent research has focused on the identification of possible DR mimetics. Energy sensing pathways, including insulin/IGF1 signaling, sirtuins, and mammalian Target of Rapamycin (mTOR), have been proposed as pathways involved in the antiaging actions of DR, and compounds that affect these pathways have been suggested to act as DR mimetics, including metformin (insulin/IGF1 signaling), resveratrol (sirtuins), and rapamycin (mTOR). Rapamycin is a promising DR mimetic because it significantly increases both health span and life span in mice. Unfortunately, rapamycin also leads to some negative effects, foremost among which is the induction of insulin resistance, potentially limiting its translation into humans. To begin clarifying the mechanism(s) involved in insulin resistance induced by rapamycin, we compared several aspects of liver metabolism in mice treated with DR or rapamycin for 6 months. Our data suggest that although both DR and rapamycin inhibit lipogenesis, activate lipolysis, and increased serum levels of nonesterified fatty acids, only DR further activates β-oxidation of the fatty acids leading to the production of ketone bodies.
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  • Keywords: Dietary Restriction, Rapamycin, β-oxidation, Metabolites
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  • Yu, Z., Wang, R., Fok, W. C., Coles, A., Salmon, A. B., & Pérez, V. I. (2015). Rapamycin and Dietary Restriction Induce Metabolically Distinctive Changes in Mouse Liver. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 70(4), 410-420. doi:10.1093/gerona/glu053
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  • 70
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  • 4
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  • Financial support was provided by National Institutional of Health (NIH) RC2 Grand Opportunity grant (AG036613, AR), The San Antonio Nathan Shock Aging Center (1P30-AG-13319, AR), NIH T32 Training Grant (AG021890, WF), and The Ellison Medical Foundation (VP), and start-up funds from the Dept. of Biochemistry and Biophysics and The Linus Pauling Institute (VP).
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