The impact of altered O-GlcNAcylation on fructose-derived metabolic derangements due to deletion of O-GlcNAc transferase in the hepatocytes.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591350
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: SEKINE Osamu 滋賀医科大学, 医学部, 助教 (00402719)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: O-GlcNAc修飾 / 肝臓 / 果糖 / 糖・脂質代謝異常

Outline of Final Research Achievements

O-GlcNAcylation is characterized by the addition of O-linked β-N-acetylglucosamine to proteins and serves as an intracellular nutrient sensor for modulating cell functions. O-GlcNAc transferase (OGT) is a critical enzyme for O-GlcNAcylation. We found out that protein O-GlcNAcylation and expression of OGT was increased in the liver fed a high-fructose diet compared to a control diet related to elevation of the lipogenesis and metabolic disorders, associating to the susceptibility to high-fructose diet.
To examine the physiological role of O-GlcNAcylation in hepatocyte biology, hepatocyte-specific OGT-deleted mice (Ogt-KO) were generated by crossbreeding Ogt-flox mice with Albumin-Cre mice. Ogt-KO showed severe hepatocellular damage, proliferation of bile ducts and fibrosis.
Our results suggest that protein O-GlcNAcylation is a key modulator for nutrient-derived metabolism in the liver, and tuning of OGT-mediated protein O-GlcNAcylation is essential to maintain hepatocyte homeostasis.

Free Research Field

代謝学