Spatiotemporal gating of SIRT1 functions by O-GlcNAcylation is essential for liver metabolic switching and prevents hyperglycemia.

ABSTRACT: Inefficient physiological transitions are known to cause metabolic disorders. Therefore, investigating mechanisms that constitute molecular switches in a central metabolic organ like the liver becomes crucial. Specifically, upstream mechanisms that control temporal engagement of transcription factors, which are essential to mediate physiological fed-fast-refed transitions are less understood. SIRT1, a NAD⁺-dependent deacetylase, is pivotal in regulating hepatic gene expression and has emerged as a key therapeutic target. Despite this, if/how nutrient inputs regulate SIRT1 interactions, stability, and therefore downstream functions are still unknown. Here, we establish nutrient-dependent O-GlcNAcylation of SIRT1, within its N-terminal domain, as a crucial determinant of hepatic f

SUBMITTER: Chattopadhyay T 

PROVIDER: S-EPMC7104039 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature