Drosophila melanogaster
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB18093 | ENA |
REPOSITORIES: ENA
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Project description:Limitation of essential amino acids, such as tyrosine or methionine/cysteine, causes upregulation of exogenous integrated transgene expression in mammalian cells. This phenomenon is mediated by histone acetylation and chromatin remodelling, since histone deacetylase (HDAC) inhibitors reproduce starvation-induced transgene upregulation and chromatin immunoprecipitation analysis of amino acid-deprived cells reveals significant changes in total core histones detectable at the CMV promoter. Expression profiling of HeLa cells starved for 5 days in medium without tyrosine or methionine/cysteine provides important information on the cellular response to amino acid deprivation and suggests the involvement of HDAC4 (class II HDAC) in transgene derepression during amino acid starvation. Total RNA obtained from HeLa and HeLaOA1myc cells (HeLa cells with a human ocular albinism type 1 (OA1)+myc tag transgene) subjected to 5 days of tyrosine or methionine/cysteine starvation compared to control cells. Twelve samples are analyzed: HeLa and HeLaOA1myc grown for 5 days in RPMI deprived of tyrosine (Y) vs. complete RPMI; technical duplicates of HeLa and HeLaOA1myc grown for 5 days in DMEM deprived of methionine/cysteine (MC) vs. complete DMEM.
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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.
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Project description:Limitation of essential amino acids, such as tyrosine or methionine/cysteine, causes upregulation of exogenous integrated transgene expression in mammalian cells. This phenomenon is mediated by histone acetylation and chromatin remodelling, since histone deacetylase (HDAC) inhibitors reproduce starvation-induced transgene upregulation and chromatin immunoprecipitation analysis of amino acid-deprived cells reveals significant changes in total core histones detectable at the CMV promoter. Expression profiling of HeLa cells starved for 5 days in medium without tyrosine or methionine/cysteine provides important information on the cellular response to amino acid deprivation and suggests the involvement of HDAC4 (class II HDAC) in transgene derepression during amino acid starvation.
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Project description:Forty percent of the US population and 1 in 6 individuals worldwide are obese, with the incidence surging globally1,2. Various dietary interventions, including carbohydrate, fat and more recently amino acid restriction, have been explored to combat this epidemic3-6. We investigated the impact of removing individual amino acids on the weight profiles of mice. Here, we show that conditional cysteine restriction resulted in the most dramatic weight loss when compared to essential amino acid restriction, amounting to 30% within one week, which was readily reversed. We found that cysteine deficiency activated the integrated stress response and oxidative stress response, which amplify each other, leading to the induction of GDF15 and FGF21, which partly explained the phenotype7-9. Surprisingly, we observed lower tissue coenzyme A (CoA), which has been considered to be extremely stable10, resulting in reduced mitochondrial functionality and metabolic rewiring. This results in energetically inefficient anaerobic glycolysis and defective TCA cycle, with sustained urinary excretion of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen rich compounds, and amino acids In summary, our investigation reveals that cysteine restriction, by depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism, and stress signaling compared to other amino acid restrictions. These findings suggest novel strategies for addressing a range of metabolic diseases and the growing obesity crisis.
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Project description:Forty percent of the US population and 1 in 6 individuals worldwide are obese, with the incidence surging globally1,2. Various dietary interventions, including carbohydrate, fat and more recently amino acid restriction, have been explored to combat this epidemic3-6. We investigated the impact of removing individual amino acids on the weight profiles of mice. Here, we show that conditional cysteine restriction resulted in the most dramatic weight loss when compared to essential amino acid restriction, amounting to 30% within one week, which was readily reversed. We found that cysteine deficiency activated the integrated stress response and oxidative stress response, which amplify each other, leading to the induction of GDF15 and FGF21, which partly explained the phenotype7-9. Surprisingly, we observed lower tissue coenzyme A (CoA), which has been considered to be extremely stable10, resulting in reduced mitochondrial functionality and metabolic rewiring. This results in energetically inefficient anaerobic glycolysis and defective TCA cycle, with sustained urinary excretion of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen rich compounds, and amino acids In summary, our investigation reveals that cysteine restriction, by depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism, and stress signaling compared to other amino acid restrictions. These findings suggest novel strategies for addressing a range of metabolic diseases and the growing obesity crisis.
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Project description:Forty percent of the US population and 1 in 6 individuals worldwide are obese, with the incidence surging globally1,2. Various dietary interventions, including carbohydrate, fat and more recently amino acid restriction, have been explored to combat this epidemic3-6. We investigated the impact of removing individual amino acids on the weight profiles of mice. Here, we show that conditional cysteine restriction resulted in the most dramatic weight loss when compared to essential amino acid restriction, amounting to 30% within one week, which was readily reversed. We found that cysteine deficiency activated the integrated stress response and oxidative stress response, which amplify each other, leading to the induction of GDF15 and FGF21, which partly explained the phenotype7-9. Surprisingly, we observed lower tissue coenzyme A (CoA), which has been considered to be extremely stable10, resulting in reduced mitochondrial functionality and metabolic rewiring. This results in energetically inefficient anaerobic glycolysis and defective TCA cycle, with sustained urinary excretion of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen rich compounds, and amino acids In summary, our investigation reveals that cysteine restriction, by depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism, and stress signaling compared to other amino acid restrictions. These findings suggest novel strategies for addressing a range of metabolic diseases and the growing obesity crisis.
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