Metabolic Inhibitors of O‐GlcNAc Transferase That Act In Vivo Implicate Decreased O‐GlcNAc Levels in Leptin‐Mediated Nutrient Sensing

Abstract: O‐Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N‐acetylglucosamine (O‐GlcNAc) residues is catalyzed by O‐GlcNAc transferase (OGT). O‐GlcNAc is conserved within mammals and is implicated in a wide range of physiological processes. Herein, we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice. These 5‐thiosugar analogues of N‐acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N‐acetylglucosamine‐6‐phosphate de‐N‐acetylase (NAGA), to generate a common OGT inhibitor within cells. We show that of these inhibitors, 2‐deoxy‐2‐N‐hexanamide‐5‐thio‐d‐glucopyranoside (5SGlcNHex) acts in vivo to induce dose‐ and time‐dependent decreases in O‐GlcNAc levels in various tissues. Decreased O‐GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety‐inducing hormone leptin, thus revealing a link between decreased O‐GlcNAc levels and nutrient sensing in peripheral tissues of mammals.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Metabolic Inhibitors of O‐GlcNAc Transferase That Act In Vivo Implicate Decreased O‐GlcNAc Levels in Leptin‐Mediated Nutrient Sensing ; volume:57 ; number:26 ; year:2018 ; pages:7644-7648 ; extent:5 ; Angewandte Chemie / International edition. International edition ; 57, Heft 26 (2018), 7644-7648 (gesamt 5)

Contributors, Places and Time

• Creator: Liu, Tai‐Wei ; Zandberg, Wesley F. ; Gloster, Tracey M. ; Deng, Lehua ; Murray, Kelsey D. ; Shan, Xiaoyang ; Vocadlo, David

Further information

• DOI: 10.1002/anie.201803254
• URN: urn:nbn:de:101:1-2022082307342591373960
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:26 AM CEST