A nexus of lipid and O-Glcnac metabolism in physiology and disease
Although traditionally considered a glucose metabolism-associated modification, the O-linked β-N-Acetylglucosamine (O-GlcNAc) regulatory system interacts extensively with lipids and is required to maintain lipid homeostasis. The enzymes of O-GlcNAc cycling have molecular properties consistent with t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.943576/full |
| _version_ | 1798035952318283776 |
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| author | Amber Lockridge John A. Hanover |
| author_facet | Amber Lockridge John A. Hanover |
| author_sort | Amber Lockridge |
| collection | DOAJ |
| description | Although traditionally considered a glucose metabolism-associated modification, the O-linked β-N-Acetylglucosamine (O-GlcNAc) regulatory system interacts extensively with lipids and is required to maintain lipid homeostasis. The enzymes of O-GlcNAc cycling have molecular properties consistent with those expected of broad-spectrum environmental sensors. By direct protein-protein interactions and catalytic modification, O-GlcNAc cycling enzymes may provide both acute and long-term adaptation to stress and other environmental stimuli such as nutrient availability. Depending on the cell type, hyperlipidemia potentiates or depresses O-GlcNAc levels, sometimes biphasically, through a diversity of unique mechanisms that target UDP-GlcNAc synthesis and the availability, activity and substrate selectivity of the glycosylation enzymes, O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). At the same time, OGT activity in multiple tissues has been implicated in the homeostatic regulation of systemic lipid uptake, storage and release. Hyperlipidemic patterns of O-GlcNAcylation in these cells are consistent with both transient physiological adaptation and feedback uninhibited obesogenic and metabolic dysregulation. In this review, we summarize the numerous interconnections between lipid and O-GlcNAc metabolism. These links provide insights into how the O-GlcNAc regulatory system may contribute to lipid-associated diseases including obesity and metabolic syndrome. |
| first_indexed | 2024-04-11T21:05:34Z |
| format | Article |
| id | doaj.art-2d252fb2a7d842a385786f7854bec4df |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-11T21:05:34Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-2d252fb2a7d842a385786f7854bec4df2022-12-22T04:03:20ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-08-011310.3389/fendo.2022.943576943576A nexus of lipid and O-Glcnac metabolism in physiology and diseaseAmber LockridgeJohn A. HanoverAlthough traditionally considered a glucose metabolism-associated modification, the O-linked β-N-Acetylglucosamine (O-GlcNAc) regulatory system interacts extensively with lipids and is required to maintain lipid homeostasis. The enzymes of O-GlcNAc cycling have molecular properties consistent with those expected of broad-spectrum environmental sensors. By direct protein-protein interactions and catalytic modification, O-GlcNAc cycling enzymes may provide both acute and long-term adaptation to stress and other environmental stimuli such as nutrient availability. Depending on the cell type, hyperlipidemia potentiates or depresses O-GlcNAc levels, sometimes biphasically, through a diversity of unique mechanisms that target UDP-GlcNAc synthesis and the availability, activity and substrate selectivity of the glycosylation enzymes, O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). At the same time, OGT activity in multiple tissues has been implicated in the homeostatic regulation of systemic lipid uptake, storage and release. Hyperlipidemic patterns of O-GlcNAcylation in these cells are consistent with both transient physiological adaptation and feedback uninhibited obesogenic and metabolic dysregulation. In this review, we summarize the numerous interconnections between lipid and O-GlcNAc metabolism. These links provide insights into how the O-GlcNAc regulatory system may contribute to lipid-associated diseases including obesity and metabolic syndrome.https://www.frontiersin.org/articles/10.3389/fendo.2022.943576/fullO-GlcNAcglycosylationhexosamine biosynthetic pathwaylipidfatty acidmetabolism |
| spellingShingle | Amber Lockridge John A. Hanover A nexus of lipid and O-Glcnac metabolism in physiology and disease Frontiers in Endocrinology O-GlcNAc glycosylation hexosamine biosynthetic pathway lipid fatty acid metabolism |
| title | A nexus of lipid and O-Glcnac metabolism in physiology and disease |
| title_full | A nexus of lipid and O-Glcnac metabolism in physiology and disease |
| title_fullStr | A nexus of lipid and O-Glcnac metabolism in physiology and disease |
| title_full_unstemmed | A nexus of lipid and O-Glcnac metabolism in physiology and disease |
| title_short | A nexus of lipid and O-Glcnac metabolism in physiology and disease |
| title_sort | nexus of lipid and o glcnac metabolism in physiology and disease |
| topic | O-GlcNAc glycosylation hexosamine biosynthetic pathway lipid fatty acid metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.943576/full |
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