Journal
FRONTIERS IN AGING
Volume 2, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fragi.2021.738512
Keywords
mTOR - mammalian target of rapamycin; C/EBP (CCAAT-enhancer-binding protein); diet-induced obesity; adefovir dipivoxil (ADV); metabolism and obesity
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Funding
- This work was supported by NIH grants R01NS98329 and P30AG013280 to MK [R01NS98329, P30AG013280]
- NIH
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This study reveals that activating C/EBP-beta LAP to regulate fat metabolism may be the mechanism behind rapamycin's anti-obesity effects, and identifies a novel drug that can be used to treat obesity and reduce the incidence of age-related diseases.
Aging and obesity are common risk factors for numerous chronic pathologies, and the compounding effects of old age and increased adiposity pose a serious threat to public health. Starting from the assumption that aging and obesity may have shared underpinnings, we investigated the antiobesogenic potential of a successful longevity intervention, the mTORC1 inhibitor rapamycin. We find that rapamycin prevents diet-induced obesity in mice and increases the activity of C/EBP-beta LAP, a transcription factor that regulates the metabolic shift to lipid catabolism observed in response to calorie restriction. Independent activation of C/EBP-beta LAP with the antiretroviral drug adefovir dipivoxil recapitulates the anti-obesogenic effects of rapamycin without reducing signaling through mTORC1 and increases markers of fat catabolism in the liver. Our findings support a model that C/EBP-beta LAP acts downstream of mTORC1 signaling to regulate fat metabolism and identifies a novel drug that may be exploited to treat obesity and decrease the incidence of age-related disease.
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