ER stress-induced leptin resistance and epigenetic mechanisms in regulating obesity

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06549
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Hiroshima University
• Principal Investigator: Ozawa Koichiro 広島大学, 医系科学研究科(薬), 教授 (10211822)
• Co-Investigator(Kenkyū-buntansha): 細井 徹 山陽小野田市立山口東京理科大学, 薬学部, 教授 (40379889)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: レプチン

Outline of Final Research Achievements

Obesity is a disease involved in environmental and genetic factors, which mechanisms remain unknown. Recent years, the ineffectiveness of leptin, an anti-obesity factor, known as “leptin resistance” has been regarded as a major cause of obesity. Homocysteine is produced with adenosine by methylation cycle and is involved in the epigenetic regulation of DNA. Therefore, in this study, we investigated the mechanism of the formation of leptin resistance by homocysteine and adenosine. As a result of this study, we evaluated the mechanism of action of these factors on the downstream of leptin signals in neurons.

Free Research Field

臨床薬理学

Academic Significance and Societal Importance of the Research Achievements

肥満は糖尿病などの生活習慣病発症の主な原因となっている。最近では肥満はCOVID19感染症による重症化のリスクを上昇させることが報告され問題視されている。したがって肥満発症機構・創薬標的を明らかにすることは、様々な肥満に付随する疾患の予防的観点からも重要と考えられる。本研究により、肥満に関わるレプチン抵抗性のメカニズムの一端が明らかになったことより、生活習慣病等の疾患の予防・治療薬創製に寄与できると考えられる。