Emerging Role of Protein O-GlcNAcylation in Liver Metabolism: Implications for Diabetes and NAFLD

O-linked b-N-acetyl-glucosaminylation (O-GlcNAcylation) is one of the most common post-translational modifications of proteins, and is established by modifying the serine or threonine residues of nuclear, cytoplasmic, and mitochondrial proteins. O-GlcNAc signaling is considered a critical nutrient sensor, and affects numerous proteins involved in cellular metabolic processes. O-GlcNAcylation modulates protein functions in different patterns, including protein stabilization, enzymatic activity, transcriptional activity, and protein interactions. Disrupted O-GlcNAcylation is associated with an abnormal metabolic state, and may result in metabolic disorders. As the liver is the center of nutrient metabolism, this review provides a brief description of the features of the O-GlcNAc signaling pathway, and summarizes the regulatory functions and underlying molecular mechanisms of O-GlcNAcylation in liver metabolism. Finally, this review highlights the role of O-GlcNAcylation in liver-associated diseases, such as diabetes and nonalcoholic fatty liver disease (NAFLD). We hope this review not only benefits the understanding of O-GlcNAc biology, but also provides new insights for treatments against liver-associated metabolic disorders.

Automated summary

O-GlcNAcylation is a common post-translational modification of proteins, which primarily occurs on serine and threonine residues of nuclear, cytoplasmic, and mitochondrial proteins. It functions as a critical nutrient sensor and influences various proteins involved in cellular metabolic processes. O-GlcNAcylation regulates protein functions through different mechanisms and disruption of this process can lead to metabolic disorders. This review focuses on the O-GlcNAc signaling pathway, its role in liver metabolism, and its implications in liver-associated diseases such as diabetes and nonalcoholic fatty liver disease (NAFLD). The review aims to enhance understanding of O-GlcNAcylation biology and provide insights for the development of treatments for liver-associated metabolic disorders.