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Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice

ABSTRACT: Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice

PROVIDER: PRJNA1071548 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27799344_1.fastq.gz	Fastqsanger.gz
	SRR27799344_2.fastq.gz	Fastqsanger.gz
	SRR27799345_1.fastq.gz	Fastqsanger.gz
	SRR27799345_2.fastq.gz	Fastqsanger.gz
	SRR27799346_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice

Project description:In the present study, we explored whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle Cth knockout (CthΔskm) mice. Metabolomics coupled with transcriptome showed that CthΔskm mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in Cth-floxed mice (Cthf/f) mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. CthΔskm+HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to Cthf/f+HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in CthΔskm+HFD mice. Omics analysis showed differential pathways enriched between CthΔskm mice and Cthf/f mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in CthΔskm+HFD mice compared to Cthf/f+HFD mice. Our data indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.

2024-05-11 | GSE254704 | GEO

Thermal proteome profilling of Ergothionine treated-cells reveals its binding to cystathionine-gamma-lyase (CSE)

Project description:Ergothioneine (ET), a dietary thione/thiol, is receiving growing attention for its possible benefits in healthy aging and metabolic resilience. Our study investigates ET's effects on healthspan in aged animals, revealing extension of lifespan and enhanced mobility in Caenorhabditis elegans, accompanied by improved stress resistance and reduced age-associated biomarkers. In aged rats, ET administration enhances exercise endurance, muscle mass, and vascularization, concomitant with higher NAD+ levels in muscle. Mechanistically, ET acts as an alternative substrate for cystathionine gamma lyase (CSE), stimulating H2S production, which increases protein persulfidation of more than 300 protein targets. Among these, protein persulfidation-driven activation of cytosolic glycerol-3-phosphate dehydrogenase (cGPDH) primarily contributes to the ET-induced NAD+ increase. ET’s effects are abolished in models lacking CSE and cGPDH, highlighting essential role of H2S signaling and protein persulfidation. These findings elucidate ET's multifaceted actions and provide insights into its therapeutic potential for combating age-related muscle decline and metabolic perturbations. To better understand the role of ET the cells, we used thermal proteome profilling of cells treated or not with ergothionine, allowing us to find new targets for the compound including CSE.

2025-01-20 | PXD051609 | Pride

Cystathionine γ-lyase downregulation contributes to hepatocyte injury and dysfunction via multiple signaling pathways by regulation of histone lysine methylation

Project description:Chronic liver disease (CLD) is prevalent globally. We sought to elucidate the molecular mechanisms governing the progress of CLD. We confirmed hepatic cystathionine γ-lyase (Cth) expression was significantly down-regulated in some CLDs. Therefore, we subsequently investigated the roles of Cth gene in the regulation of hepatic function and underlying mechanisms by using Cth knockout mice. Furthermore, we found that Cth deficiency resulted in one-carbon unit reprogramming, and betaine was one of key metabolites in one-carbon reprogramming, which caused changed histone lysine methylation and thereby leading to dysregulation of PPARα, PGC-1α, IRF8 and IRF9, the transcriptional factors governing metabolism, mitochondrial function and apoptosis. Our data immediately highlight a new potential target for therapy of some CLDs.

2024-10-17 | GSE279401 | GEO

Dietary restriction transforms the mammalian protein sulfhydrome in a tissue-specific and cystathionine γ-lyase-dependent manner

Project description:Hydrogen sulfide (H2S) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SSnH). Despite the known importance of persulfidation on relatively few identified proteins, tissue-specific sulfhydrome profiles and their associated functions are not well characterized, specifically under conditions known to modulate H2S production. We hypothesized that dietary restriction (DR), which increases lifespan and can boost H2S production, expands tissue-specific sulfhydromes. Here, we found protein persulfidation was enriched in liver, kidney, muscle, and brain but decreased in heart of young and aged male mice under two forms of DR, with DR promoting persulfidation in numerous metabolic and aging-related pathways. Mice lacking H2S producing enzyme cystathionine γ-lyase (CGL) had overall decreased tissue protein persulfidation and failed to functionally augment sulfhydromes in response to DR. Overall, we defined tissue- and CGL-dependent sulfhydromes and how diet transforms their makeup, underscoring the breadth for DR and H2S to impact biological processes and organismal health.

2021-01-25 | PXD022956 | Pride

Dietary restriction transforms the mammalian protein sulfhydrome in a tissue-specific and cystathionine γ-lyase-dependent manner

2021-01-25 | PXD022954 | Pride

Dietary restriction transforms the mammalian protein sulfhydrome in a tissue-specific and cystathionine γ-lyase-dependent manner

2021-01-25 | PXD022888 | Pride

FBXW7 coordinates postprandial muscle glucose metabolism and maintenance of skeletal muscle mass

Project description:In this study, we show that muscle-specific inactivation of FBXW7 elicits striking defects in postprandial glucose metabolism and failure to maintain skeletal muscle mass in adult mice. Further, mice lacking FBXW7 exhibited impaired endurance capacity and exacerbated HFD-induced insulin resistance and postprandial hyperglycemia. At the mechanistic level, RNAseq and quantitative proteomic analysis revealed global effects of FBXW7 deficiency on skeletal muscle transcriptome and proteome. This work illustrates a prominent role of FBXW7 in integrating postprandial nutritional signals to coordinate glucose metabolism and muscle mass maintenance.

2024-06-21 | GSE140503 | GEO

Skeletal Muscle Transcriptomics

Project description:Skeletal Muscle Transcriptomics

| PRJNA532382 | ENA

Mass spectrometry-based analysis of the TBC1D4 interactome in human skeletal muscle

Project description:Insulin-stimulated muscle glucose uptake is a key process to alleviate hyperglycemia. This process depends on the redistribution of glucose transporters to the muscle surface membrane following phosphorylation of TBC1D1 and TBC1D4. Genetic evidence from a TBC1D4 loss-of-function mutation in human skeletal muscle is associated with an increased risk of type 2 diabetes (T2D). However, little is known about the potential regulating interactors of TBC1D4 in skeletal muscle. Here, we sought to identify interactors of TBC1D4 in human skeletal muscle by an unbiased proteomics approach. We detected 76 proteins as candidate TBC1D4 interactors, whereof 12 were regulated by insulin stimulation including known proteins involved in glucose metabolism (e.g. 14-3-3 proteins and ACTN4). TBC1D1 also co-precipitated with TBC1D4 and vice versa in both human and mouse skeletal muscle. This interaction was not regulated by insulin or exercise in young healthy lean individuals. In contrast, we observed an altered interaction as well as compromised insulin-stimulated phospho-regulation of the TBC1D1-TBC1D4 complex in muscle of obese individuals with T2D. In conclusion, we provide a list of TBC1D4 interactors in human and mouse skeletal muscle. These protein interactors serve as potential regulators of TBC1D4 function and thus insulin-stimulated glucose uptake in skeletal muscle.

2022-03-01 | PXD026225 | Pride

Cell composition and gene-expression dynamics of skeletal muscle regeneration after contraction-induced injury

Project description:Small-molecule activators targeting the allosteric drug and metabolite (ADaM) site of AMPK enhance insulin-independent glucose uptake in skeletal muscle and promote blood glucose lowering in preclinical models of hyperglycemia. The regulatory AMPKγ subunit plays a central role in energy sensing, and the skeletal muscle-selective γ3 isoform is essential for AMP/ZMP-induced glucose uptake, but not for ADaM site activators. We hypothesized that the predominant γ1 isoform is required for ADaM site activator-stimulated glucose uptake in skeletal muscle.

2025-12-02 | GSE306977 | GEO

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