Functional analysis of TRIF-mediated innate immune signaling in hypothalamic inflammation-induced dysregulation of food intake

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Toyama Prefectural Institute for Pharmaceutical Research
• Principal Investigator: Watanabe Yasuharu 富山県薬事総合研究開発センター, その他部局等, 主任研究員 (80646307)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 視床下部炎症 / 自然免疫 / 肥満

Outline of Final Research Achievements

Recent accumulating evidence suggests that toll like receptor 4 (TLR4) and the adaptor protein MyD88 induce hypothalamic inflammation, which inhibits leptin-induced anorexia and promotes hyperphagia, obesity, and metabolic syndrome.
We found that TLR4-MyD88- and TLR3-independent TLR adaptor protein TRIF signaling pathway was involved in high-fat diet (HFD)-induced hypothalamic inflammation and hyperphagia. TRIF-dependent STING singling, adaptor protein in the cytosolic DNA sensing pathway, induced hypothalamic inflammation and impaired leptin singling in hypothalamus. These results suggested that STING-TRIF singling contributes of hypothalamic inflammation and leptin resistance under HFD treatment.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

これまで考えられているTLR4-MyD88B経路よりもSTING-TRIFシグナル経路が、視床下部炎症に深く関与することを見出した。今後STING-TRIFシグナルを誘導する上流分子や責任細胞の同定により、摂食調節異常の新規メカニズムを提唱でき、自制が困難な過食性肥満の解明に貢献できると考える。