ArticleMolecular metabolism2018
Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity.
Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 84 citations in OpenAlex.
- Mitochondrial membrane lipid cardiolipin controls fiber-type adaptations in aging muscle via estrogen-related receptor γ.Nature aging · 2026Article
- Chemical biology tools for the O-GlcNAc modification: Determining systems-level functions and druggability.Current opinion in chemical biology · 2026Review
- Impact of captivity on gut microbiota, tracheal microbiota and metabolic pathways in wild chipmunks.BMC microbiology · 2026Article
- Nobiletin Ameliorates Skeletal Muscle Performance in D-Galactose-Induced Aging Mice by Boosting Aerobic Metabolism.Food science & nutrition · 2026Article
- Epigenetic Changes Associated With Obesity-related Metabolic Comorbidities.Journal of the Endocrine Society · 2025Review
- Insulin- and exercise-induced phosphoproteomics of human skeletal muscle identify REPS1 as a regulator of muscle glucose uptake.Cell reports. Medicine · 2025Article
- Upregulation of OGT-mediated EZH2 O-GlcNAcylation Promotes Human Umbilical Vein Endothelial Cell Proliferation, Invasion, Migration, and Tube Formation in Gestational Diabetes Mellitus.Cell biochemistry and biophysics · 2025Article
- O-GlcNAcylation in Endocrinology: The Sweet Link.Endocrinology · 2025Review
- Housing Temperature Impacts the Systemic and Tissue-Specific Molecular Responses to Cancer in Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- O-linked β-N-acetylglucosamine modification in diabetic foot ulcer pathogenesis.Burns & trauma · 2025Review
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- O-GlcNAcylation in ischemic diseases.Frontiers in pharmacology · 2024Review
- O-GlcNAcylation of SIRT1 Protects against Cold Stress-Induced Skeletal Muscle Damage via Amelioration of Mitochondrial Homeostasis.International journal of molecular sciences · 2022Article
- O-GlcNAcylation is a gatekeeper of porcine myogenesis.Journal of animal science · 2022Article
- RNA binding motif protein 3 (RBM3) promotes protein kinase B (AKT) activation to enhance glucose metabolism and reduce apoptosis in skeletal muscle of mice under acute cold exposure.Cell stress & chaperones · 2022Article
- Posttranslational modifications in diabetes: Mechanisms and functions.Reviews in endocrine & metabolic disorders · 2022Review
- ProteinMetabolites · 2022Review
- Protein O-GlcNAcylation and the regulation of energy homeostasis: lessons from knock-out mouse models.Journal of biomedical science · 2022Review
- Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity.Science advances · 2022Article
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveGiven that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT), the enzyme that mediates O-GlcNAcylation, in skeletal muscle.
methodsWe assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry. Whole body insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique and tissue-specific glucose uptake was subsequently evaluated. Tissues were used for histology, qPCR, Western blot, co-immunoprecipitation, and chromatin immunoprecipitation analyses.
resultsWe found elevated levels of O-GlcNAc-modified proteins in obese, type 2 diabetic people compared with well-matched obese and lean controls. Muscle-specific OGT knockout mice were lean, and whole body energy expenditure and insulin sensitivity were increased in these mice, consistent with enhanced glucose uptake and elevated glycolytic enzyme activities in skeletal muscle. Moreover, enhanced glucose uptake was also observed in white adipose tissue that was browner than that of WT mice. Interestingly, mKO mice had elevated mRNA levels of Il15 in skeletal muscle and increased circulating IL-15 levels. We found that OGT in muscle mediates transcriptional repression of Il15 by O-GlcNAcylating Enhancer of Zeste Homolog 2 (EZH2).
conclusionsElevated muscle O-GlcNAc levels paralleled insulin resistance and type 2 diabetes in humans. Moreover, OGT-mediated signaling is necessary for proper skeletal muscle metabolism and whole-body energy homeostasis, and our data highlight O-GlcNAcylation as a potential target for ameliorating metabolic disorders.
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