Mus musculus
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ABSTRACT:
PROVIDER: PRJNA258564 | ENA |
REPOSITORIES: ENA
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Project description:Regulatory logic of the coupled diurnal and feeding cycles in the mouse liver
| PRJNA258563 | ENA
Project description:Regulatory logic of the coupled diurnal and feeding cycles in the mouse liver [DNase-seq, ChIP-seq]
| PRJNA258229 | ENA
Project description:Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by this interconnectedness is associated with metabolic disease. Here we tested the interactions between clocks in two critical components of organismal metabolism – liver and skeletal muscle – by rescuing clock function either in each organ separately, or in both organs simultaneously, in otherwise clock-less mice. Experiments revealed that individual clocks are partially sufficient for tissue glucose metabolism, yet the connections between both tissue clocks coupled with daily feeding rhythms maximizes systemic glucose tolerance. This synergy relies in part on local transcriptional control of the glucose machinery, feeding-responsive signals such as insulin, and metabolic cycles that connect the muscle and liver. We posit that spatiotemporal mechanisms of muscle and liver play an essential role in the maintenance of systemic glucose homeostasis, and that disrupting this diurnal coordination can contribute to the metabolic disease.
2023-05-29 | GSE228389 | GEO
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
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.
2026-07-06 | PXD066866 | Pride
Project description:Background: Cellular iron homeostasis is regulated by iron regulatory proteins (IRP1 and IRP2) that sense iron levels (and other metabolic cues) and modulate mRNA translation or stability via interaction with iron regulatory elements (IREs). IRP2 is viewed as the primary regulator in liver, yet our previous datasets showing diurnal rhythms for certain IRE-containing mRNAs suggest a nuanced temporal control mechanism. The purpose of this study is to gain insights into the daily regulatory dynamics across IRE-bearing mRNAs, specific IRP involvement, and underlying systemic and cellular rhythmicity cues in mouse liver. Results: We uncover high-amplitude diurnal oscillations in the regulation of key IRE containing transcripts in liver, compatible with maximal IRP activity at the onset of the dark phase. Although IRP2 protein levels also exhibit some diurnal variations and peak at the light-dark transition, ribosome profiling in IRP2-deficient mice reveals that maximal repression of target mRNAs at this time-point still occurs. We further find that diurnal regulation of IRE-containing mRNAs can continue in the absence of a functional circadian clock as long as feeding is rhythmic. Conclusions: Our findings suggest temporally controlled redundancy in IRP activities, with IRP2 mediating regulation of IRE-containing transcripts in the light phase and redundancy, conceivably with IRP1, at dark onset. Moreover, we highlight the significance of feeding-associated signals in driving rhythmicity. Our work highlights the dynamic nature and regulatory complexity in a metabolic pathway that had previously been considered well-understood.
2024-05-01 | GSE243134 | GEO
Project description:Liver circadian clock and daily rhythmic transcriptome are highly responsive to metabolic cues generated from daily feeding activity. The mechanisms that mediate metabolic inputs to the whole rhythmic transcriptome are still under investigation. Here, we explored the role of O-GlcNAcylation, a nutrient-sensitive post-translational modification (PTM) that integrates circadian and metabolic signals, in the diurnal regulation of nuclear proteins. We found daily oscillation of overall nuclear protein O-GlcNAcylation in the liver of mice subjected to natural night time-restricted feeding (NRF). O-GlcNAcomic analysis revealed that 11.54% of 719 O-GlcNAcylated proteins are rhythmically O-GlcNAcylated. Proteins involved in gene expression were enriched, suggesting rhythmic O-GlcNAcylation may directly shape diurnal transcriptome. Furthermore, we showed that rhythmic O-GlcNAcylation could indirectly modulate diurnal transcriptome by interacting with phosphorylation. Specifically, several proteins harboring O-GlcNAcylation-phosphorylation interplay motif exhibit rhythmic O-GlcNAcylation and phosphorylation. For example, O-GlcNAcylation may occur at a phosphor-degron of a key circadian transcriptional activator, circadian locomotor output cycles kaput (CLOCK), regulating the stability and transcriptional output of CLOCK. Lastly, unnatural day time-restricted feeding (DRF) dampens O-GlcNAcylation rhythm, suggesting the disruption of diurnal transcriptome could be mediated by protein O-GlcNAcylation. In summary, our results provide mechanistic insights into metabolic regulation of diurnal transcriptome at PTM level and shed light on the deleterious effects of improper mealtimes.
2024-03-27 | MSV000094417 | MassIVE
Project description:Daily biological rhythms are orchestrated by a combination of the intrinsic circadian clock and external food/feeding-related signals which influence metabolism in health and disease. Understanding how and to which extent both circadian and fasting/feeding rhythms contribute to regulating daily physiology and metabolism is therefore an important ongoing effort. We generated a comprehensive proteomics dataset performing large scale time-series analysis of mouse liver obtained from feeding restricted mice over 2 full days with 16 time points in total, including as a first, a shorter post-feeding sampling-rate focus. Using our label-free absolute quantitative proteomics platform we obtained timelines with very few missing values (>99% data completeness) for over 4000 mouse liver proteoforms using 1D-LC-MS analysis of all time points and replicates (48 samples in total) allowing for robust statistical testing, as well as over 8000 mouse liver proteoforms using online 2D-LC-MS analysis of pooled replicates, providing additional depth of detection. Together our dataset provides an important resource recapitulating and extending current datasets. Our extra focus on post-feeding time points revealed a highly dynamic third metabolic period not previously observed with respect to more classic diurnal rhythmicity, providing an important addition to current knowledge.
2021-01-22 | PXD008944 | Pride
Project description:The liver secretes most circulating proteins, which are critical for inter-organ communication and systemic energy homeostasis. However, the regulatory mechanisms governing hepatic protein secretion are largely unknown. Using proteomics approaches in humans and mice, we here demonstrate that hepatic protein secretion follows a 24-hour rhythm which is modulated by the timing of food intake. Rhythmic variations in the expression of secretory pathway proteins, involved in protein glycosylation and folding in the endoplasmic reticulum and Golgi apparatus, mediate this process. We find that feeding rhythms and the circadian clock protein BMAL1 regulate diurnal hepatic protein secretion by driving glycogen breakdown which generates glycosylation substrates. Rhythmic secretion was attenuated in a mouse model of obesity and affected by genetic variants associated with glycogen storage disease and congenital disorders of glycosylation. Our study reveals a mechanistic link between glycogen-derived metabolites and protein secretion, thereby connecting nutrient intake with fundamental liver functions.
2026-01-06 | PXD058564 | Pride