Elucidation of gastrointestinal motility disorders caused by dietary obesity and of new treatment development

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K17945
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Health Science University
• Principal Investigator: Satoshi Shimo 健康科学大学, 健康科学部, 准教授 (80734607)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 糖尿病 / 肥満 / 糖尿病自律神経障害 / 消化管運動障害 / アウエルバッハ神経叢 / 筋間神経叢 / SBF-SEM / 3次元再構築

Outline of Final Research Achievements

Obesity induced in mice through high fat diet (HFD) revealed the following three points. (1) In HFD-fed mice, NOS, substance P, and calbindin in the myenteric plexus were significantly decreased, while NOS was increased after phlorizin treatment. (2) In HFD-fed mice, accumulation of synaptic vesicles in axon varicosities was decreased, but increased synaptic accumulation vesicle and formation of lateral branches were observed after phlorizin treatment. (3) Delayed gastrointestinal transit time was observed in HFD-fed mice. The HFD induced a decrease in synaptic vesicles in the myenteric plexus during the prediabetic period, when glucose intolerance began. Furthermore, it was suggested that phlorizin treatment may act to improve peristalsis as well as restore lost axonal varicosities of the myenteric plexus in HFD-fed obese mice.

Free Research Field

解剖学関連

Academic Significance and Societal Importance of the Research Achievements

世界の肥満人口は急速に増えており、日本でも欧米型(高脂肪)の食事とともに、肥満を背景とした2型糖尿病患者が増加傾向であり、大きな社会的問題となっている。また、糖尿病の合併症ではしびれなどの感覚神経障害以外にも、下痢や便秘などの消化器症状を高頻度で引き起こし、日常生活が著しく制限されるため社会的な損失も大きい。しかし、これらの消化器症状の発症機序は不明な点が多く、対症的な治療となるため新規薬剤の開発が求められている。我々の研究により、腸管神経叢を標的とした消化管機能改善薬を開発することができれば、糖尿病の新たな治療法として臨床への応用・発展が大いに期待でき、社会的意義は大きい。