| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| 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.
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