Project description:Co-migration / spiking experiment to confirm the retention time of drug analogs detected in HNRC fecal samples with those in microbial cultures
Project description:Co-migration / spiking experiment to confirm the retention time of drug analogs detected in HNRC fecal samples with those in microbial cultures
Project description:Time-restricted feeding improves metabolic health independently of dietary macronutrient composition or energy restriction. To understand the mechanisms underpinning the effects of time-restricted feeding, we investigated the metabolic and transcriptomic profile of skeletal muscle and serum samples from 11 overweight/obese men. In muscle, 4-10% of transcripts and 14% of metabolites were periodic, with the amplitude of the metabolites lower after time-restricted feeding. Core clock genes were unaltered by either intervention, while time-restricted feeding induced rhythmicity of genes related to lipid and amino acid transport. In serum, 49-65% of the metabolites had diurnal rhythms across both conditions, with the majority being lipids. Time-restricted feeding shifted the skeletal muscle metabolite profile from predominantly lipids to amino acids. Our results show time-restricted feeding differentially affects the amplitudes and rhythmicity of serum and skeletal muscle metabolites, and regulates the rhythmicity of genes controlling lipid and amino acid transport, without perturbing the core clock.
Project description:Metabolomic analyses reveal the specific array of metabolites present in a cell type or tissue at any given time. Multiple lines of evidence indicate that metabolites provide a readout of ongoing cellular functions, and changes in the metabolome correlate with specific biological processes1–4 as seen, for instance, during cellular differentiation. These changes are potentially associated with the regulation of signaling pathways and gene expression networks that are critical to alter cellular identity5–7. However, it is less clear whether specific metabolites or metabolic pathways can drive changes in cellular identity. To identify metabolites engaged with cell state transitions, we performed metabolomic analyses at the earliest stages of cellular differentiation and uncovered metabolites transiently upregulated just as the first transcriptional changes emerged. Specifically, we observed a wave of one-carbon metabolism conserved between three different multipotent stem cell types. Treatment of fully differentiated cells with these metabolites caused the loss of mature identity and transition toward progenitor-like states, thus demonstrating that the metabolome plays a causative role in initiating and modulating cell fate. Our studies reveal a metabolic intervention that can reprogram cellular phenotypes and could potentially be applied in regenerative medicine applications
Project description:Metabolomic analyses reveal the specific array of metabolites present in a cell type or tissue at any given time. Multiple lines of evidence indicate that metabolites provide a readout of ongoing cellular functions, and changes in the metabolome correlate with specific biological processes1–4 as seen, for instance, during cellular differentiation. These changes are potentially associated with the regulation of signaling pathways and gene expression networks that are critical to alter cellular identity5–7. However, it is less clear whether specific metabolites or metabolic pathways can drive changes in cellular identity. To identify metabolites engaged with cell state transitions, we performed metabolomic analyses at the earliest stages of cellular differentiation and uncovered metabolites transiently upregulated just as the first transcriptional changes emerged. Specifically, we observed a wave of one-carbon metabolism conserved between three different multipotent stem cell types. Treatment of fully differentiated cells with these metabolites caused the loss of mature identity and transition toward progenitor-like states, thus demonstrating that the metabolome plays a causative role in initiating and modulating cell fate. Our studies reveal a metabolic intervention that can reprogram cellular phenotypes and could potentially be applied in regenerative medicine applications