The elucidation of the role of NIK in estrogen deficiency-induced diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09890
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: University of East Asia
• Principal Investigator: Mukai Satoru 東亜大学, その他の研究科, 准教授 (90467887)
• Co-Investigator(Kenkyū-buntansha): 自見 英治郎 九州大学, 歯学研究院, 教授 (40276598)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 閉経後肥満 / 炎症 / RANKL / NIK

Outline of Final Research Achievements

Menopausal women are susceptible to visceral obesity. Circulating levels of receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) are elevated in an animal model of menopause. RANKL activates a pivotal mediator of inflammatory responses, the NF-κB pathway. Here, we investigated whether RANKL-induced non-canonical NF-κB pathway activation induces inflammation and lipid accumulation in adipose tissues. We therefore analyzed aly/aly mice, in which the non-canonical NF-κB pathway is not activated. A postmenopausal obesity model was generated by ovariectomy and subsequent high-fat and high-sucrose diet feeding. In aly/aly mice, serum RANKL levels were elevated, and hepatic lipid accumulation and adipocyte hypertrophy were suppressed. Furthermore, aly/aly mice showed protection from glucose intolerance and insulin resistance. These findings indicate that non-canonical NF-κB pathway activation via serum RANKL elevation contributes to postmenopausal obesity.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

閉経後、女性は代謝異常（メタボリックシンドローム）のリスクを増加させる肥満になりやすい。しかしながら、閉経後に誘発される脂質蓄積のメカニズムについて詳細に明らかにはされていない。我々は、NIKを病態発症のキー分子と想定し、サイトカインRANKLに着目して閉経後肥満の発症機構の一端を明らかにした。この成果は、骨粗鬆症やメタボリックシンドロームの発症機序を明らかにしたという学術的な意義を持つ。さらに、上記疾患の予防や治療における創薬へ向けた基盤となる知見である。