Caloric restriction effects on liver mTOR signaling are time-of-day dependent

Aging
Richa TulsianRoman Kondratov

Abstract

The regulation of mechanistic target of rapamycin (mTOR) signaling contributes to the metabolic effects of a calorie restriction (CR) diet. We assayed the effect of CR on the activity of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) in the liver of mice at six different times across the day. CR effects on mTORC1 and mTORC2 activities were time-of-day dependent. CR induced mTORC1 activity at one time, reduced at two times and has no effect during other times. CR induced mTORC2 activity at one time of the day and has no effects at other times. Circadian clocks are implemented in the regulation of mTOR signaling in mammals and mechanisms of CR. We assayed the effect of CR on mTOR signaling in the liver of mice deficient for circadian transcriptional regulators BMAL1 and CRYs. The CR induced suppression of mTORC1 activity was observed in both clock mutants, while up regulation of mTORC2 was observed in the liver of CRY deficient but not in the liver of BMAL1 deficient mice. Our finding revealed that CR has different time dependent effect on the activity of mTOR complexes 1 and 2 and suggest that circadian clock protein BMAL1 is involved in the up regulation of mTORC2 upon CR in mammals.

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Citations

Apr 30, 2019·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Daniel Mauvoisin
Feb 6, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nikkhil VelingkaarRoman V Kondratov
Mar 7, 2021·Biology·Sonal A Patel, Roman V Kondratov
Apr 3, 2021·IScience·Mehrshad Sadria, Anita T Layton
May 19, 2021·Nature Communications·Victoria A Acosta-RodríguezJoseph S Takahashi
Jun 3, 2021·Nutrients·Alda AttinàLaura Di Renzo
May 28, 2021·Frontiers in Nutrition·Sergej M Ostojic

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Methods Mentioned

BETA
protein assay

Software Mentioned

GraphPad
SPSS Statistics
Image Studio Lite

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