ArticleBiochimica et biophysica acta. Molecular basis of disease2018
Consumption of a high fat diet promotes protein O-GlcNAcylation in mouse retina via NR4A1-dependent GFAT2 expression.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Discovering diabetes complications-related microRNAs: meta-analyses and pathway modeling approach.BMC medical genomics · 2025Pooled it
- FOXO6 inhibits SMURF2-mediated ubiquitination and degradation of NR4A1 to promote retinal pigment epithelial cell ferroptosis in diabetic retinopathy.Journal of cell communication and signaling · 2026Article
- Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review.Cell death discovery · 2025Review
- Protein O-GlcNAcylation in reproductive biology and the impact of metabolic disease.Human reproduction update · 2025Review
- Exploring the metabolic signaling network of GFPT in cancer.Cell death discovery · 2025Review
- High-fat diet alters retinal lipid composition and gene expression networks in mice.BMC biology · 2025Article
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Article
- Regulation of protein O-GlcNAcylation by circadian, metabolic, and cellular signals.The Journal of biological chemistry · 2024Review
- Review
- Nutrient-sensitive protein O-GlcNAcylation shapes daily biological rhythms.Open biology · 2022Review
- Review
- Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy.Current diabetes reviews · 2022Article
- A nexus of lipid andFrontiers in endocrinology · 2022Review
- O-GlcNAcylation links oncogenic signals and cancer epigenetics.Discover oncology · 2021Review
- Different Sources of Dietary Magnesium Supplementation Reduces Oxidative Stress by Regulation Nrf2 and NF-κB Signaling Pathways in High-Fat Diet Rats.Biological trace element research · 2021Article
- Transcriptomic analysis of the mouse retina after acute and chronic normobaric and hypobaric hypoxia.Scientific reports · 2021Article
- GFAT and PFK genes show contrasting regulation of chitin metabolism in Nilaparvata lugens.Scientific reports · 2021Article
- Impacts of high fat diet on ocular outcomes in rodent models of visual disease.Experimental eye research · 2021Review
- Retinol-binding protein 4 mRNA translation in hepatocytes is enhanced by activation of mTORC1.American journal of physiology. Endocrinology and metabolism · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The incidence of type 2 diabetes, the most common cause of diabetic retinopathy (DR), is rapidly on the rise in developed countries due to overconsumption of calorie rich diets. Using an animal model of diet-induced obesity/pre-diabetes, we evaluated the impact of a diet high in saturated fat (HFD) on O-GlcNAcylation of retinal proteins, as dysregulated O-GlcNAcylation contributes to diabetic complications and evidence supports a role in DR. Protein O-GlcNAcylation was increased in the retina of mice fed a HFD as compared to littermates receiving control chow. Similarly, O-GlcNAcylation was elevated in retinal Müller cells in culture exposed to the saturated fatty acid palmitate or the ceramide analog Cer6. One potential mechanism responsible for elevated O-GlcNAcylation is increased flux through the hexosamine biosynthetic pathway (HBP). Indeed, inhibition of the pathway's rate-limiting enzyme glutamine-fructose-6-phosphate amidotransferase (GFAT) prevented Cer6-induced O-GlcNAcylation. Importantly, expression of the mRNA encoding GFAT2, but not GFAT1 was elevated in both the retina of mice fed a HFD and in retinal cells in culture exposed to palmitate or Cer6. Notably, expression of nuclear receptor subfamily 4 group A member 1 (NR4A1) was increased in the retina of mice fed a HFD and NR4A1 expression was sufficient to promote GFAT2 mRNA expression and O-GlcNAcylation in retinal cells in culture. Whereas palmitate or Cer6 addition to culture medium enhanced NR4A1 and GFAT2 expression, chemical inhibition of NR4A1 transactivation repressed Cer6-induced GFAT2 mRNA expression. Overall, the results support a model wherein HFD increases retinal protein O-GlcNAcylation by promoting NR4A1-dependent GFAT2 expression.
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