TY - JOUR
T1 - Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila
AU - Katewa, Subhash D.
AU - Akagi, Kazutaka
AU - Bose, Neelanjan
AU - Rakshit, Kuntol
AU - Camarella, Timothy
AU - Zheng, Xiangzhong
AU - Hall, David
AU - Davis, Sonnet
AU - Nelson, Christopher S.
AU - Brem, Rachel B.
AU - Ramanathan, Arvind
AU - Sehgal, Amita
AU - Giebultowicz, Jadwiga M.
AU - Kapahi, Pankaj
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/1/12
Y1 - 2016/1/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84955335015&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2015.10.014
DO - 10.1016/j.cmet.2015.10.014
M3 - 学術論文
C2 - 26626459
AN - SCOPUS:84955335015
SN - 1550-4131
VL - 23
SP - 143
EP - 154
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -