The role of calcitonin gene-related peptide (CGRP) in regulation of intestinal fat absorption

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07127
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kitasato University
• Principal Investigator: Hosono Kanako 北里大学, 医学部, 講師 (80532556)
• Co-Investigator(Kenkyū-buntansha): 伊藤 義也 北里大学, 医学部, 准教授 (40203187)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脂肪吸収 / 腸管リンパ管 / CGRP / RAMP1 / 肥満

Outline of Final Research Achievements

Lacteals, lymphatic vessels at the center of each intestinal villus, play an important role in fat absorption. The present study was examined whether CGRP (Calcitonin gene-related peptide) and its receptor, RAMP1 (receptor activity modifying protein 1), are involved in fat absorption via the lacteals. RAMP1 KO mice fed HFD for 8 weeks gained higher body weights compared with WT mice and developed severe obesity. In HFD fed RAMP1 KO mice, the structures of lacteals and the fat absorption function were compromised, suggesting that CGRP / RAMP1 is involved in the regulation of dietary fat absorption by lacteals.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

これまで乳糜管における脂肪吸収のメカニズムは未解明であった。本研究では高脂肪食によって誘導された乳糜管可塑性にはCGRP/RAMP1が関与する可能性を検証するもので、知覚神経由来の神経ペプチドが肥満に関与するかどうかに焦点をあてて解明を進めるのが本研究の特徴である。脂肪吸収、脂肪循環の最初の関門である乳糜管機能にCGRP/RAMP1経路の役割を明らかにすることができれば、肥満・メタボリック症候群の発症への治療介入につながることが期待される。