Mechanisms underlying enhanced GLP-1 response in diet-induced obesity

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K05860
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: Hokkaido University
• Principal Investigator: Hira Tohru 北海道大学, 農学研究院, 准教授 (10396301)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 消化管内分泌系 / GLP-1 / 食事誘導性肥満

Outline of Final Research Achievements

We discovered an increased meal-induced GLP-1 secretion in a diet-induced obesity model rats. We aimed to elucidate the underlying mechanism. In a genetically diabetic model, long-term administration of an obesity-inducing diet did not induce an adaptive increase in GLP-1 secretion. The adaptive increase in GLP-1 secretion occurred in the distal small intestine, and an increased GLP-1 secretion response was observed for carbohydrates, lipids, and proteins. Since there were no differences in GLP-1 content or the number of GLP-1-producing cells in the small intestinal mucosa, it was hypothesized that the adaptive increase in GLP-1 secretion may be attributed to enhanced nutrient sensitivity in GLP-1-producing cells.

Free Research Field

栄養生理学

Academic Significance and Societal Importance of the Research Achievements

消化管において栄養素を感知して、消化管ホルモンを分泌することで食後の生理応答をコントロールする消化管内分泌系を理解することは、食事を利用して生体応答をコントロールできる技術開発に資する。また、病態における消化管内分泌系の関与を理解し、その分子メカニズムを知ることは、病態の予防、改善に貢献できる。本研究では血糖値や食欲をコントロールする消化管モルモンであるGLP-1の分泌機構の食環境への適応機構の一端を明らかにすることで、学術的・社会的貢献を目指した。