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NADH inhibition of SIRT1 links energy state to transcription during time-restricted feeding

Levine, Daniel C. (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
Kuo, Hsin-Yu (författare)
Northwestern Univ, Dept Chem, Evanston, IL USA.;Northwestern Univ, Dept Biomed Engn, Evanston, IL USA.;Northwestern Univ, Dept Cell & Mol Biol, Evanston, IL USA.
Hong, Hee-Kyung (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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Cedernaes, Jonathan, Docent, 1985- (författare)
Uppsala universitet,Transplantation och regenerativ medicin,Institutionen för medicinsk cellbiologi,Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA
Hepler, Chelsea (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
Wright, Alexandra G. (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
Sommars, Meredith A. (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
Kobayashi, Yumiko (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
Marcheva, Biliana (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
Gao, Peng (författare)
Northwestern Univ, Feinberg Sch Med, Robert H Lurie Canc Ctr Metabol Core, Chicago, IL USA.
Ilkayeva, Olga R. (författare)
Duke Univ Sch Med, Dept Med, Div Endocrinol Metab & Nutr, Duke Mol Physiol Inst, Durham, NC USA.
Omura, Chiaki (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
Ramsey, Kathryn M. (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
Newgard, Christopher B. (författare)
Duke Univ Sch Med, Dept Med, Div Endocrinol Metab & Nutr, Duke Mol Physiol Inst, Durham, NC USA.
Barish, Grant D. (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
Peek, Clara Bien (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.;Northwestern Univ, Feinberg Sch Med, Dept Biochem & Mol Genet, Chicago, IL USA.
Chandel, Navdeep S. (författare)
Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL USA.
Mrksich, Milan (författare)
Northwestern Univ, Dept Chem, Evanston, IL USA.;Northwestern Univ, Dept Biomed Engn, Evanston, IL USA.;Northwestern Univ, Dept Cell & Mol Biol, Evanston, IL USA.
Bass, Joseph (författare)
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA Northwestern Univ, Dept Chem, Evanston, IL USA.;Northwestern Univ, Dept Biomed Engn, Evanston, IL USA.;Northwestern Univ, Dept Cell & Mol Biol, Evanston, IL USA. (creator_code:org_t)
2021-12-13
2021
Engelska.
Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 3:12, s. 1621-1632
Relaterad länk:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
https://www.nature.c...
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD+, a cosubstrate of the class III histone deacetylase sirtuin 1 (SIRT1) that associates with clock transcription factors. Although NAD+ also participates in redox reactions, the extent to which NAD(H) couples nutrient state with circadian transcriptional cycles remains unknown. Here we show that nocturnal animals subjected to time-restricted feeding of a calorie-restricted diet (TRF-CR) only during night-time display reduced body temperature and elevated hepatic NADH during daytime. Genetic uncoupling of nutrient state from NADH redox state through transduction of the water-forming NADH oxidase from Lactobacillus brevis (LbNOX) increases daytime body temperature and blood and liver acyl-carnitines. LbNOX expression in TRF-CR mice induces oxidative gene networks controlled by brain and muscle Arnt-like protein 1 (BMAL1) and peroxisome proliferator-activated receptor alpha (PPARα) and suppresses amino acid catabolic pathways. Enzymatic analyses reveal that NADH inhibits SIRT1 in vitro, corresponding with reduced deacetylation of SIRT1 substrates during TRF-CR in vivo. Remarkably, Sirt1 liver nullizygous animals subjected to TRF-CR display persistent hypothermia even when NADH is oxidized by LbNOX. Our findings reveal that the hepatic NADH cycle links nutrient state to whole-body energetics through the rhythmic regulation of SIRT1.

Ämnesord

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

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