期刊
FRONTIERS IN ENDOCRINOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2022.943576
关键词
O-GlcNAc; glycosylation; hexosamine biosynthetic pathway; lipid; fatty acid; metabolism; obesity; homeostasis
资金
- NIDDK intramural research program [ZIADK060103]
The O-GlcNAc regulatory system interacts extensively with lipids and is essential for maintaining lipid homeostasis. Hyperlipidemia affects O-GlcNAc levels through various mechanisms and is associated with obesity and metabolic dysregulation.
Although traditionally considered a glucose metabolism-associated modification, the O-linked beta-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.
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