Elucidation of new tissue and molecular bases causing obesity

• Project/Area Number: 18H02967
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Kyushu University
• Principal Investigator: Jimi Eijiro 九州大学, 歯学研究院, 教授 (40276598)
• Co-Investigator(Kenkyū-buntansha): 松田 美穂 九州大学, 歯学研究院, 准教授 (40291520) ; 高 靖 九州大学, 歯学研究院, 助教 (40585882) ; 溝上 顕子 九州大学, 歯学研究院, 准教授 (70722487) ; 片桐 岳信 埼玉医科大学, 医学部, 教授 (80245802)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2018: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 肥満 / 緩やかな炎症 / NF-κB / N􏰅F-κB / NF-kB / 摂食中枢

Outline of Final Research Achievements

Metabolic diseases caused by obesity significantly reduce quality of life and are accompanied by life-threatening complications. In recent years, it has been reported that phosphorylation of p65 plays an important role in the transcriptional regulation of NF-κB, and in particular, phosphorylation of the serine 534 (S534) residue at the C-terminal has been considered to be extremely important. Therefore, we generated S534A knock-in mice that are not phosphorylated. When S534A mice were maintained on a high-fat diet (HFD), body weight was gained by increasing both the amount of food and water consumed. Furthermore, it showed decreased glucose tolerance and insulin resistance. Histologically, fatty liver was exhibited when S534A mice were bred in HFD. Furthermore, when S534A mice were maintained over 20 weeks, renal and uterine edema was frequently observed regardless of whether they were maintained on a normal diet or HFD.

Academic Significance and Societal Importance of the Research Achievements

我々の研究成果は、p65の安定性制御を介した持続的活性化がPara-Inflammationを意味することを示した。さらにp65のリン酸化制御が、生活習慣病の発症機序の解明とともに、予防法や治療法の開発につながることが期待できる。