Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Diurnal regulation of Acyl-CoA synthetase 3 (ACSF3) governs rhythmic mitochondrial lysine-malonylation and daily hepatic metabolism

ABSTRACT: Hepatic daily rhythms are coordinated by feeding and the molecular circadian clock, ensuring metabolic homeostasis. Disrupted feeding schedules promote circadian misalignment and metabolic disease but the underlying mechanisms remain unknown. Post-translational modifications have emerged as key regulators of circadian metabolic outputs. In this framework, mitochondria constitute a central hub, integrating metabolic rhythms, feeding cycles and the circadian clock. Here, we show that the mitochondrial enzyme Acyl-CoA-synthetase-family-member-3 (ACSF3) oscillates in phase with different feeding schedules to drive rhythmic lysine-malonylation and coordinate daily hepatic metabolism. Hepatic ACSF3 knockdown affected lysine-malonylation rhythms, decreased fasting glycemia, insulin sensitivity and AKT phosphorylation. It also shifted lipid oxidation from mitochondria to peroxisomes, enhanced de novo lipogenesis and triglyceride synthesis, while increasing diurnal autophagy. Integrated multi-omics profiling uncovered specific lysine-malonylation targets in glycolysis, the TCA cycle, fatty-acid oxidation and autophagy. Our findings establish ACSF3 as a critical link between feeding time, protein malonylation, and diurnal liver metabolism.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Daniel Mauvoisin

LAB HEAD: Daniel Mauvoisin

PROVIDER: PXD066866 | Pride | 2026-07-06

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	TE-A7-01_sh-Ctl.raw	Raw
	TE-A7-02_sh-Ctl.raw	Raw
	TE-A7-03_sh-Ctl.raw	Raw
	TE-A7-04_sh-Ctl.raw	Raw
	TE-A7-05_sh-Ctl.raw	Raw

Items per page:

1 - 5 of 34

Similar Datasets

Diurnal regulation of Acyl-CoA synthetase 3 (ACSF3) governs rhythmic mitochondrial lysine-malonylation and daily hepatic metabolism

Project description:Hepatic daily rhythms are coordinated by feeding and the molecular circadian clock, ensuring metabolic homeostasis. Disrupted feeding schedules promote circadian misalignment and metabolic disease but the underlying mechanisms remain unknown. Post-translational modifications have emerged as key regulators of circadian metabolic outputs. In this framework, mitochondria constitute a central hub, integrating metabolic rhythms, feeding cycles and the circadian clock. Here, we show that the mitochondrial enzyme Acyl-CoA-synthetase-family-member-3 (ACSF3) oscillates in phase with different feeding schedules to drive rhythmic lysine-malonylation and coordinate daily hepatic metabolism. Hepatic ACSF3 knockdown affected lysine-malonylation rhythms, decreased fasting glycemia, insulin sensitivity and AKT phosphorylation. It also shifted lipid oxidation from mitochondria to peroxisomes, enhanced de novo lipogenesis and triglyceride synthesis, while increasing diurnal autophagy. Integrated multi-omics profiling uncovered specific lysine-malonylation targets in glycolysis, the TCA cycle, fatty-acid oxidation and autophagy. Our findings establish ACSF3 as a critical link between feeding time, protein malonylation, and diurnal liver metabolism.

2026-07-07 | PXD066863 | Pride

Diurnal regulation of Acyl-CoA synthetase 3 (ACSF3) governs rhythmic mitochondrial lysine-malonylation and daily hepatic metabolism

Project description:Hepatic daily rhythms are coordinated by feeding and the molecular circadian clock, ensuring metabolic homeostasis. Disrupted feeding schedules promote circadian misalignment and metabolic diseases but the underlying mechanisms remain scarce. Post-translational modifications have emerged as key regulators of circadian metabolic outputs. Here, we show that the mitochondrial enzyme Acyl-CoA synthetase family member 3 (ACSF3) oscillates in phase with different feeding schedules to drive rhythmic lysine-malonylation and coordinate daily hepatic metabolism. Hepatic Acsf3 knockdown drastically affected lysine-malonylation rhythms, decreased fasting glycemia, insulin sensitivity and AKT phosphorylation indicative of perturbed glucose homeostasis. Concomitantly, Acsf3 knockdown shifted lipid oxidation from mitochondria to peroxisomes, enhanced lipogenesis and triglyceride synthesis, while increasing diurnal autophagy. Multi-omics profiling uncovered specific lysine-malonylation targets in glycolysis, the TCA cycle, fatty-acid oxidation and autophagy. Our findings uncover hepatic ACSF3 as a pivotal molecular nexus that integrates feeding time with dynamic protein lysine-malonylation and orchestrates the diurnal rhythm of liver metabolism.

2026-07-07 | GSE330452 | GEO

Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver.

Project description:Diurnal oscillations of gene expression controlled by the circadian clock underlie rhythmic physiology across most living organisms. Although such rhythms have been extensively studied at the level of transcription and mRNA accumulation, little is known about the accumulation patterns of proteins. Here, we quantified temporal profiles in the murine hepatic proteome under physiological light–dark conditions using stable isotope labeling by amino acids quantitative MS. To measure the daily accumulation of proteins, we designed an SILAC MS experiment, in which total protein extracts were harvested from C57BL/6J mice every 3 h for 2 d (eight samples per day). Relative protein abundance in each of 16 samples was quantified against a common reference sample labeled using the SILAC method. The generated mass spectra allowed the identification of a total of 5,827 distinct proteins, of which 70% yielded relative measurements in at least 8 of 16 samples. Our analysis identified over 5,000 proteins, of which several hundred showed robust diurnal oscillations with peak phases enriched in the morning and during the night and related to core hepatic physiological functions. Combined mathematical modeling of temporal protein and mRNA profiles indicated that proteins accumulate with reduced amplitudes and significant delays, consistent with protein half-life data. Moreover, a group comprising about one-half of the rhythmic proteins showed no corresponding rhythmic mRNAs, indicating significant translational or posttranslational diurnal control. Such rhythms were highly enriched in secreted proteins accumulating tightly during the night. Also, these rhythms persisted in clock-deficient animals subjected to rhythmic feeding, suggesting that food-related entrainment signals influence rhythms in circulating plasma factors

2014-08-08 | PXD001211 | Pride

Diurnal feeding behaviour drives 24h rhythms within intestinal epithelial cells and the gut microbiome

Project description:Gut function exhibits 24h (circadian) rhythmicity, in part driven by intrinsic clocks within intestinal epithelial cells (IECs). The gut microbiome exhibits 24h rhythms in composition and function, which are important for maintenance of metabolic and immune health. We determined the influence of feeding behaviour on the colonic circadian landscape using an interval feeding paradigm, whereby food intake was partitioned equally across the 24h day. RNAseq analysis revealed that the IEC cell intrinsic clock persists in the absence of diurnal feeding rhythms, however a subset of transcripts lose rhythmicity, demonstrating that feeding driven cell extrinsic temporal cues contribute significantly to maintenance of the rhythmic gut transcriptome. Interval fed mice lost rhythmicity in secretory IgA and within the microbiota and microbial derived short chain fatty acids. This work highlights the importance of daily rhythms in feeding behaviour for maintenance of rhythmic processes within the gut, with implications for metabolic and immune health.

2025-11-20 | E-MTAB-14883 | biostudies-arrayexpress

GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency

Project description:Disruptions in circadian rhythms are associated with increased risk of developing metabolic diseases. General control nonderepressible 2 (GCN2), a primary sensor of amino acid insufficiency and activator of the integrated stress response (ISR), has emerged as a conserved regulator of the circadian clock in multiple organisms. The objective of this study was to examine diurnal patterns in hepatic ISR activation in the liver and whole-body rhythms in metabolism. We hypothesized that GCN2 activation cues hepatic ISR signaling over a natural 24 h feeding fasting cycle. To address our objective, wild type (WT) and whole body Gcn2 knockout (GCN2 KO) mice were housed in metabolic cages and provided free access to either a Control or leucine-devoid diet (LeuD) for 8-days in total darkness. On the last day, blood and livers were collected at circadian time (CT) 3 and CT15. In livers of WT mice, GCN2 phosphorylation followed a diurnal pattern that was guided by intracellular branched chain amino acid concentrations (r2=0.93). Feeding LeuD to WT mice increased hepatic ISR activation at CT15 only. Diurnal oscillation in hepatic ISR signaling, the hepatic transcriptome including lipid metabolic genes, and triglyceride concentrations were substantially reduced or absent in GCN2 KO mice. Further, mice lacking GCN2 were unable to maintain circadian rhythms in whole body energy expenditure, respiratory exchange ratio and physical activity when fed LeuD. In conclusion, GCN2 activation functions to maintain diurnal ISR activation in the liver and has a vital role in the mechanisms by which nutrient stress affects whole-body metabolism.

2024-08-27 | GSE262319 | GEO

The effects of temporally restricted feeding on hepatic gene expression of Cry1, Cry2 double KO mice

Project description:Restricted feeding impacts the hepatic circadian clock of WT mice. Cry1, Cry2 double KO mice lack a circadian clock and are thus expected to show rhythmical gene expression in the liver. Imposing a temporally restricted feeding schedule on these mice shows how the hepatic circadian clock and rhythmic food intake regulate rhythmic transcription in parallel Cry1, Cry2 double KO mice were entrained either to ad libitum or temporally restricted feeding (tRF) schedules. Food was made available to mice under the tRF regimen only between ZT(CT)1 and ZT(CT)9. Mice were then released into constant darkness while the respective feeding schedules were still maintained. Liver tissue was collected on the second day of constant darkness at the indicated timepoints. Total RNA was extracted and 5ug of RNA was used in the standard Affymetrix protocol for amplification, labeling and hybridization

2009-11-23 | E-GEOD-13062 | biostudies-arrayexpress

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver [RNASeq]

Project description:Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. While rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in wild-type and Bmal1 deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic genes expression, Bmal1 deletion having surprisingly more impact at the post-transcriptional level. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5â-TOP sequences and for genes involved in mitochondrial activity and harboring a TISU motif. The increased translation efficiency of 5â-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion impacts also amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. RNA-Seq from total RNA of mouse liver during the dirunal cycle. Time-series mRNA profiles of wild type (WT) and Bmal -/- mice under ad libitum and night restriced feeding regimen were generated by deep sequencing.

2015-11-10 | E-GEOD-73552 | biostudies-arrayexpress

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver [RNASeq]

Project description:Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. While rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in wild-type and Bmal1 deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic genes expression, Bmal1 deletion having surprisingly more impact at the post-transcriptional level. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5’-TOP sequences and for genes involved in mitochondrial activity and harboring a TISU motif. The increased translation efficiency of 5’-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion impacts also amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.

2015-11-10 | GSE73552 | GEO

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver [Ribosome Profiling]

Project description:Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. While rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in wild-type and Bmal1 deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic genes expression, Bmal1 deletion having surprisingly more impact at the post-transcriptional level. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5’-TOP sequences and for genes involved in mitochondrial activity and harboring a TISU motif. The increased translation efficiency of 5’-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion impacts also amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.

2015-11-10 | GSE73553 | GEO

Inter-layer and inter-subject variability of circadian gene expression in human skin

Project description:This work reports 24 h gene expression rhythms in two skin layers, epidermis and dermis, in a cohort of young, healthy adults, who maintained natural, regular sleep-wake schedules. 10% of the expressed genes showed such diurnal rhythms at the population level, of which only a third differed between the two layers. Amplitude and phases of diurnal gene expression varied more across subjects than layers, with amplitude being more variable than phases. Expression amplitudes in the epidermis were larger and more subject-variable, while they were smaller and more consistent in the dermis. Core clock gene expression was similar across layers at the population-level, but were heterogeneous in their variability across subjects. This work provides a valuable resource to advance our understanding of human skin and presents a novel methodology to quantify sources of variability in human circadian rhythms.

2022-12-12 | GSE205155 | 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