NADH Inhibition of SIRT1 Links Energy State to Transcription During Time-Restricted Feeding
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ABSTRACT:
PROVIDER: PRJNA635381 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13553400.fastq.gz | Fastqsanger.gz | |||
| SRR13553401.fastq.gz | Fastqsanger.gz | |||
| SRR13553402.fastq.gz | Fastqsanger.gz | |||
| SRR13553403.fastq.gz | Fastqsanger.gz | |||
| SRR13553404.fastq.gz | Fastqsanger.gz |
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Project description: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.
2021-10-08 | GSE151281 | GEO
Project description: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.
| S-EPMC8688143 | biostudies-literature
Project description:The main aim of this experiment was to investigate gene expression on human adipose tissue after two different 4-week energy-restricted diets. Our questions consisted in understanding how gene expression was linked to clinical parameters of obese patients and whether the two diets were discriminated this data. The subjects were randomly allocated, in a cross-over design, to two periods of 4 weeks of an energy restricted isocaloric diet of 1200 kcal as either a conventional diet (LC-CONV) or a special energy restricted diet compensated by proteins (LC-P-LGI). The two nutritional periods were separated by a wash-out interval of 8 weeks. The samples who contain a K in their name correspond to the LC-P-LGI diet while those who contain a C correspond to LC-CONV diet. Total RNA obtained from isolated human adipose tissue of 12 subjects at 6 different time points (0, 5, 30, 90, 95 and 120 days).
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