TitleRapamycin and dietary restriction induce metabolically distinctive changes in mouse liver.
Publication TypeJournal Article
Year of Publication2015
AuthorsYu Z, Wang R, Fok WC, Coles A, Salmon AB, Perez VI
JournalJ Gerontol A Biol Sci Med Sci
Date Published2015 Apr
KeywordsAnimals, Antibiotics, Antineoplastic, Biomarkers, Caloric Restriction, Glucose-6-Phosphate, Lactic Acid, Liver, Longevity, Male, Mice, Mice, Inbred C57BL, Sirolimus

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.

Alternate JournalJ. Gerontol. A Biol. Sci. Med. Sci.
PubMed ID24755936
PubMed Central IDPMC4447794
Grant List1P30-AG-13319 / AG / NIA NIH HHS / United States
AG021890 / AG / NIA NIH HHS / United States
AG036613 / AG / NIA NIH HHS / United States