Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NADH Inhibition of SIRT1 Links Energy State to Transcription During Time-Restricted Feeding

ABSTRACT: In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD+ a co-substrate of the class III histone deacetylase SIRT1 that associates with clock transcription factors. While 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 nighttime 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 BMAL1 and PPARa 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE151281 | GEO | 2021/10/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression profile of SoNar-high and SoNar-low B-cell acute lymphoblastic leukemia (B-ALL) cells

Project description:To dissect the metabolic state of B-ALL cells, we have developed a genetically encoded fluorescent sensor (SoNar) for tracking cytosolic NADH and NAD+ redox states and constructed the transgenic mouse. Based on the NADH/NAD+ ratio, we have sorted SoNar-high and SoNar-low B-ALL cells to employ whole genome microarray expression profiling as a discovery platform to identify genes with the potential to regulate the metabolism of B-ALL cells.

2018-02-06 | GSE110111 | GEO

Gene expression profile of SoNar-high and SoNar-low fetal liver blood cells

Project description:To dissect the metabolic state of fetal liver HSCs, we have developed a genetically encoded fluorescent sensor (SoNar) for tracking cytosolic NADH and NAD+ redox states and constructed the transgenic mouse. Based on the NADH/NAD+ ratio, we have sorted SoNar-high and SoNar-low fetal liver blood cells to employ whole genome microarray expression profiling as a discovery platform to identify genes with the potential to regulate fetal liver HSC metabolism.

2018-02-06 | GSE110109 | GEO

Gene expression profile of SoNar-high and SoNar-low B-cell acute lymphoblastic leukemia (B-ALL) cells

2020-05-25 | GSE151106 | GEO

Prolonged fasting times reap greater geroprotective effects when combined with caloric restriction in adult female mice

Project description:Emerging new evidence highlights the importance of prolonged daily fasting periods for the health and survival benefits of calorie restriction (CR) and time-restricted feeding (TRF) in male mice; however, little is known about the impact of these feeding regimens in females. We placed 14-month-old female mice on five different dietary regimens, either CR or TRF with different feeding windows, and determined the effects of these regimens on physiological responses, progression of neoplasms and inflammatory diseases, serum metabolite levels, and lifespan. Compared with TRF feeding, CR elicited a robust systemic response, as it relates to energetics and healthspan metrics, a unique serum metabolomics signature in overnight fasted animals, and was associated with an increase in lifespan. These results indicate that daytime (rest-phase) feeding with prolonged fasting periods initiated late in life confer greater benefits when combined with imposed lower energy intake.

2024-05-14 | MTBLS790 | MetaboLights

Overexpression of CYB5R3 and NQO1, two NAD+ producing enzymes, mimics aspects of caloric restriction

Project description:Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH-dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age-associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through up-regulation of these NADH-dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD+/sirtuin pathway. The results highlight the importance of these NAD+ producers for the promotion of health and extended lifespan.

2018-07-31 | GSE108379 | GEO

Physiological responses of Saccharopolyspora erythraea towards perturbation of intracellular NADH/NAD+

Project description:Knowledge about effects of cofactor perturbation on cellular metabolism is scarce with respect to Saccharopolyspora erythraea. The water-forming NADH oxidase (NOX) from Streptococcus pneumonia was expressed in S.erythraea E3, an important industrial strain for erythromycin production, at three different levels to investigate effects of intracellular redox status on secondary metabolism. NOX expression reduced the intracellular [NADH]/[NAD+] ratios significantly, although with a strong constitutive promoter NOX function was limited due to the shortage of oxygen. We demonstrated the negative correlation between [NADH]/[NAD+] ratios and biosynthesis of erythromycin in S.erythraea, but a positive correlation between the redox ratios and pigment production as well. We furthermore completed next-generation RNA sequencing of E3 and two NOX-expression strains. The transcription results showed that transfer processes of carbohydrates, DNA and chemical groups were altered resulting in metabolic shifts to supply more NADH for NOX fully functioning. Additionally, redox status affected transcription of several genes by allosteric effects on their transcription initiation. Specifically, transcriptional analysis along with enzymatic assay suggested that redox status influenced biosynthesis of erythromycin indirectly by allosteric effects on biosynthesis of the secondary messenger, c-di-GMP. The present work provides a basis for future cofactor manipulation in S.erythraea for further improvement of erythromycin production.

2020-08-04 | GSE144067 | GEO

Gene expression profile in Liver, skeletal muscle, brown and white adipose tissues in mice after different interventions

Project description:SIRT1 is a NAD+-dependent protein deacetylase. SIRT1 plays key roles in metabolic regulation and adaptation. In this study, we wanted to compare gene expression profile in SIRT1 overexpressing mice to WT mice submitted to different intervention (caloric restriction and exercise training) in different tissues (liver, skeletal muscle, brown and white adipose tissues). SIRT1 transgenic model has already been described (Pfluger et al., 2008). Here we used homozygote transgenic mice which had been backcrossed to C57Bl/6N background. 3 months old WT and SIRT1tg mice were fed with a low fat diet. After sacrifice, total mRNA obtained from brown adipose were used for microarray. Caloric restriction (CR) : everyother day feeding during 3 months Exercise training (EX) : mice were housed in running wheel cages during 10 weeks

2015-07-14 | E-GEOD-70857 | biostudies-arrayexpress

SIRT1 but not its increased expression is essential for lifespan extension in caloric restricted mice.

Project description:The SIRT1 deacetylase is one of the best-studied potential mediators of some of the anti-aging effects of calorie restriction (CR); but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild type mice on an ad libitum diet. Here we report that median lifespan extension in CR heterozygote SIRT1+/- mice was identical (51%) to that observed in wild type mice but SIRT1+/- mice displayed a higher frequency of some certain pathologies. Although larger studies in different genetic backgrounds are necessary , these results provide strong initial evidence for the requirement of SIRT1 for the anti-aging effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension. Key words: SIRT1, caloric restriction, lifespan, anti-aging 2-5 month old male mice of 3 different genotypes (SIRT1+/+, SIRT1+/-, and SIRT1-/-) that had normal, reduced or no expression of SIRT1 were treated with either a 40% caloric restricted diet (CR) or an ad libitum diet (AL). 2-4 replicates of each experimental condition were used in the analysis.

2014-04-25 | E-GEOD-46895 | biostudies-arrayexpress

NAD+/NADH Redox Alterations Reconfigure Metabolism and Rejuvenate Senescent Human Mesenchymal Stem Cells In Vitro

Project description:Human mesenchymal stem cells (hMSCs) promote endogenous tissue regeneration and have become a promising candidate for cell therapy. However, in vitro culture expansion of hMSCs induces a rapid decline of stem cell properties through replicative senescence. Here we characterize metabolic profiles of hMSCs during expansion. We show that alterations of cellular nicotinamide adenine dinucleotide (NAD+ /NADH) redox balance and activity of the Sirtuin (Sirt) family enzymes regulate cellular senescence of hMSCs. Treatment with NAD+ precursor nicotinamide increases the intracellular NAD+ level and re-balances the NAD+ /NADH ratio, with enhanced Sirt-1 activity in hMSCs at high passage, partially restores mitochondrial fitness and rejuvenates senescent hMSCs. By contrast, human fibroblasts exhibit limited senescence as their cellular NAD+ /NADH balance is comparatively stable during expansion. These results indicate a potential metabolic and redox connection to replicative senescence in adult stem cells and identify NAD+ as a metabolic regulator that distinguishes stem cells from mature cells. This study also suggests potential strategies to maintain cellular homeostasis of hMSCs in clinical applications.

2021-09-09 | PXD022395 | Pride

Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism

Project description:Hepatic metabolic derangements are key components in the development of fatty liver, insulin resistance, and atherosclerosis. SIRT1, a NAD+-dependent protein deacetylase, is an important regulator of energy homeostasis in response to nutrient availability. Here we demonstrate that hepatic SIRT1 regulates fatty acid metabolism by positively regulating PPAR-alpha. Hepatocyte-specific deletion of SIRT1 impairs PPAR-alpha signaling and decreased fatty acid beta-oxidation in the liver. When challenged with a high-fat diet, liver-specific SIRT1 knockout mice develop hepatic steatosis, hepatic inflammation, and endoplasmic reticulum stress. Taken together, our data indicate that SIRT1 plays a vital role in the regulation of hepatic lipid homeostasis.

2009-04-07 | GSE14921 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data