| Literature DB >> 26626459 |
Subhash D Katewa1, Kazutaka Akagi2, Neelanjan Bose2, Kuntol Rakshit3, Timothy Camarella2, Xiangzhong Zheng4, David Hall2, Sonnet Davis2, Christopher S Nelson2, Rachel B Brem2, Arvind Ramanathan2, Amita Sehgal4, Jadwiga M Giebultowicz3, Pankaj Kapahi5.
Abstract
Endogenous circadian clocks orchestrate several metabolic and signaling pathways that are known to modulate lifespan, suggesting clocks as potential targets for manipulation of metabolism and lifespan. We report here that the core circadian clock genes, timeless (tim) and period (per), are required for the metabolic and lifespan responses to DR in Drosophila. Consistent with the involvement of a circadian mechanism, DR enhances the amplitude of cycling of most circadian clock genes, including tim, in peripheral tissues. Mass-spectrometry-based lipidomic analysis suggests a role of tim in cycling of specific medium chain triglycerides under DR. Furthermore, overexpression of tim in peripheral tissues improves its oscillatory amplitude and extends lifespan under ad libitum conditions. Importantly, effects of tim on lifespan appear to be mediated through enhanced fat turnover. These findings identify a critical role for specific clock genes in modulating the effects of nutrient manipulation on fat metabolism and aging.Entities:
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Year: 2015 PMID： 26626459 PMCID： PMC4715572 DOI： 10.1016/j.cmet.2015.10.014
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287