{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:53:51Z","timestamp":1793105631491,"version":"4.5.0"},"reference-count":349,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"Although traditionally considered a glucose metabolism-associated modification, the O<\/jats:italic>-linked \u03b2-N-Acetylglucosamine (O-<\/jats:italic>GlcNAc) regulatory system interacts extensively with lipids and is required to maintain lipid homeostasis. The enzymes of O-<\/jats:italic>GlcNAc cycling have molecular properties consistent with those expected of broad-spectrum environmental sensors. By direct protein-protein interactions and catalytic modification, O<\/jats:italic>-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-<\/jats:italic>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<\/jats:italic>-GlcNAc Transferase (OGT) and O<\/jats:italic>-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<\/jats:italic>-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-<\/jats:italic>GlcNAc metabolism. These links provide insights into how the O-<\/jats:italic>GlcNAc regulatory system may contribute to lipid-associated diseases including obesity and metabolic syndrome.<\/jats:p>","DOI":"10.3389\/fendo.2022.943576","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T08:35:47Z","timestamp":1661848547000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["A nexus of lipid and O-Glcnac metabolism in physiology and disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Amber","family":"Lockridge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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