Elucidation of the molecular mechanisms and treatment against physiological factor/ER stress-induced obesity/metabolic syndrome

2022 Fiscal Year Final Research Report

• Project/Area Number: 18KK0463
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Tokyo University of Science, Yamaguchi (2020-2022); Hiroshima University (2018-2019)
• Principal Investigator: Hosoi Toru 山陽小野田市立山口東京理科大学, 薬学部, 教授 (40379889)
• Project Period (FY): 2019 – 2022
• Keywords: レプチン

Outline of Final Research Achievements

An obesity is related to the ineffectiveness of leptin, i.e; the formation of leptin resistance. We have revealed that endoplasmic reticulum stress is involved in the cause of leptin resistance. In this study, we investigated the mechanism of leptin resistance. As a result, IRE1α, one of the endoplasmic reticulum stress sensor proteins, interacted with the OB-R leptin receptor and affected leptin signaling. On the other hand, glial derived factor, released during endoplasmic reticulum stress/chronic inflammation, induced leptin resistance by acting on the downstream pathway of leptin signaling without affecting OB-R leptin receptor activity.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

肥満は生活習慣病などの原因となることが知られており、肥満の発症機構を明らかにすることは、それらの疾患の予防や治療薬開発において重要である。本研究で明らかにした肥満のメカニズムに関する基礎的知見は、これらの疾患発症予防や治療に貢献できる可能性がある。