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
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.
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.
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
Project description:Temporally restricted feeding is known to impact the circadian clock. This dataset shows the effects of temporally restricted feeding on the hepatic transcriptome.
Project description:Meal timing is essential in synchronization of circadian rhythms in different organ systems through clock-dependent and -independent mechanisms. Adipose tissue is a critical metabolic and endocrine organ whose circadian clock and transcriptome can be reset by meal timing. However, it remains largely unexplored how circadian rhythms in adipose tissue are organized in time-restricted feeding that intervenes meal timing. Here, we applied quantitative phospho-proteomics to characterize circadian features associated with ad libitum feeding (ALF), day/inactive phase-restricted feeding (DRF) and night/active phase-restricted feeding (NRF) in female mice.
Project description:Temporally restricted feeding has a profound effect on the hepatic circadian clock. While the circadian clock is largely unaffected by by extensive fasting, many transcripts are known to be affected by a fasting paradigm. This dataset shows the effect of extensive fasting on dynamic gene expression in the liver
Project description:Temporally restricted feeding has a profound effect on the circadian clock. Fasting and feeding paradigms are known to influence hepatic transcription. This dataset shows the dynamic effects of refeeding mice after a 24hour fasting period.
