Trans-kingdom control of microbiota diurnal oscillations promotes metabolic homeostasis
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Project description:Trans-kingdom mimicry underlies ribosome customization by a poxvirus kinase
Sujata Jha*1, Madeline G. Rollins*1, Gabriele Fuchs2, Dean J. Procter1, Elizabeth A. Hall3, Kira Cozzolino3, Peter Sarnow4, Jeffrey N. Savas3 and Derek Walsh1
1Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. 2The RNA Institute, Department of Biological Sciences, University of Albany-SUNY, Albany, NY 12222, USA. 3Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. 4Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2017-03-21 | MSV000080661 | MassIVE
Project description:Brown adipose tissue (BAT) burns fatty acids to produce heat, and shows diurnal oscillation with peak activity in glucose and triglyceride-derived fatty acid uptake at wakening. To gain further insight in the diurnal regulation of metabolic BAT activity, we performed chromatin immunoprecipitation sequencing (ChIP-seq) on pooled interscapular (i)BAT samples collected from chow-fed male C57BL/6J mice (10 weeks old) exposed to mild cold (22°C) at 3-hour intervals throughout a 24-hour period (n=8 mice per time point). All mice were entrained to a 12h:12h light:dark cycle, and therefore time is denoted as Zeitgeber Time (ZT) in which ZT0 indicates the onset of the light (active) phase.
2022-04-16 | GSE197261 | GEO
Project description:Brown adipose tissue (BAT) burns fatty acids to produce heat, and shows diurnal oscillation with peak activity in glucose and triglyceride-derived fatty acid uptake at wakening. To gain further insight in the diurnal regulation of metabolic BAT activity, we performed RNA-sequencing (RNA-seq) on interscapular (i)BAT samples collected from chow-fed male C57BL/6J mice (10 weeks old) exposed to mild cold (22°C) at 3-hour intervals throughout a 24-hour period (n=4 mice per time point). All mice were entrained to a 12h:12h light:dark cycle, and therefore time is denoted as Zeitgeber Time (ZT) in which ZT0 indicates the onset of the light (active) phase.
2022-04-16 | GSE182045 | GEO
Project description:Mitochondria are major suppliers of cellular energy through nutrients oxidation. Little is known about the mechanisms that enable mitochondria to cope with changes in nutrient supply and energy demand that naturally occur throughout the day. To address this question, we applied mass-spectrometry based quantitative proteomics on isolated mitochondria from mice sacrificed throughout the day and identified extensive oscillations in the mitochondrial proteome. We found that rate-limiting mitochondrial enzymes that process lipids and carbohydrates accumulate in a diurnal manner and dependent on the clock proteins PER1/2. In this conjuncture, we uncovered daily oscillations in mitochondrial respiration that peak during different times of the day in response to different nutrients. Notably, the diurnal regulation of mitochondrial respiration was blunted in mice lacking PER1/2 or upon nutritional challenge such as high fat diet. We propose that the clock proteins PER1/2 optimize mitochondrial metabolism to daily changes in energy supply/demand and thereby serve as a rheostat for mitochondrial nutrient utilization.
2018-10-17 | PXD001732 | Pride
Project description:<p><strong>OBJECTIVE: </strong>Brown adipose tissue (BAT) burns fatty acids (FAs) to produce heat, and shows diurnal oscillation in glucose and triglyceride (TG)-derived FA-uptake, peaking around wakening. Here we aimed to gain insight in the diurnal regulation of metabolic BAT activity.</p><p><strong>METHODS: </strong>RNA-sequencing, chromatin immunoprecipitation (ChIP)-sequencing and lipidomics analyses were performed on BAT samples of wild type C57BL/6J mice collected at 3-h intervals throughout the day. Knockout and overexpression models were used to study causal relationships in diurnal lipid handling by BAT.</p><p><strong>RESULTS: </strong>We identified pronounced enrichment of oscillating genes involved in extracellular lipolysis in BAT, accompanied by oscillations of FA and monoacylglycerol content. This coincided with peak lipoprotein lipase (Lpl) expression, and was predicted to be driven by peroxisome proliferator-activated receptor gamma (PPARγ) activity. ChIP-sequencing for PPARγ confirmed oscillation in binding of PPARγ to Lpl. Of the known LPL-modulators, angiopoietin-like 4 (Angptl4) showed the largest diurnal amplitude opposite to Lpl, and both Angptl4 knockout and overexpression attenuated oscillations of LPL activity and TG-derived FA-uptake by BAT.</p><p><strong>CONCLUSIONS: </strong>Our findings highlight involvement of PPARγ and a crucial role of ANGPTL4 in mediating the diurnal oscillation of TG-derived FA-uptake by BAT, and imply that time of day is essential when targeting LPL activity in BAT to improve metabolic health.</p>
2023-11-15 | MTBLS4082 | MetaboLights
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