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NADH inhibition of ...
NADH inhibition of SIRT1 links energy state to transcription during time-restricted feeding
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- Levine, Daniel C. (författare)
- Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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- 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.
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- 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
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- Hepler, Chelsea (författare)
- Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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- Wright, Alexandra G. (författare)
- Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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- Sommars, Meredith A. (författare)
- Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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- Kobayashi, Yumiko (författare)
- Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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- Marcheva, Biliana (författare)
- Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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- Gao, Peng (författare)
- Northwestern Univ, Feinberg Sch Med, Robert H Lurie Canc Ctr Metabol Core, Chicago, IL USA.
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- Ilkayeva, Olga R. (författare)
- Duke Univ Sch Med, Dept Med, Div Endocrinol Metab & Nutr, Duke Mol Physiol Inst, Durham, NC USA.
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- Omura, Chiaki (författare)
- Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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- Ramsey, Kathryn M. (författare)
- Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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- Newgard, Christopher B. (författare)
- Duke Univ Sch Med, Dept Med, Div Endocrinol Metab & Nutr, Duke Mol Physiol Inst, Durham, NC USA.
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- Barish, Grant D. (författare)
- Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Dept Med, Chicago, IL 60208 USA.
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- 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.
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- Chandel, Navdeep S. (författare)
- Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL USA.
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- 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.
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- 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.
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Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 3:12, s. 1621-1632
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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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Till lärosätets databas
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Levine, Daniel C ...
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Kuo, Hsin-Yu
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Hong, Hee-Kyung
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Cedernaes, Jonat ...
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Hepler, Chelsea
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Wright, Alexandr ...
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visa fler...
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Sommars, Meredit ...
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Kobayashi, Yumik ...
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Marcheva, Bilian ...
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Gao, Peng
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Ilkayeva, Olga R ...
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Omura, Chiaki
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Ramsey, Kathryn ...
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Newgard, Christo ...
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Barish, Grant D.
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Peek, Clara Bien
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Chandel, Navdeep ...
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Mrksich, Milan
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Bass, Joseph
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visa färre...
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Uppsala universitet