3-B-P-039 〇細野 加奈子^1,2、伊藤 義也^1,2、別當 朋広³、田邉 美奈²、山下 敦²、鎌田 真理子^1,2、畑中 公^1,2、馬嶋 正隆^1,4、天野 英樹^1,2 Kanako Hosono^1,2, Yoshiya Ito^1,2, Tomohiro Betto³, Mina Tanabe², Atsushi Yamashita², Mariko Kamata^1,2, Koh Hatanaka^1,2, Masataka Majima^1,4, Hideki Amano^{1,2 1}北里大・医、²北里大・院医・分子薬理、³北里大・医・消内、⁴神奈川工科大・健康医療科・病態治療 ¹Dept. Pharm., Sch. Med., Kitasato Univ., ²Dept. Mol. Pharm., Grad. Sch. Med., Kitasato Univ., ³Dept.Gastroenterol, Sch. Med., Kitasato Univ., ⁴Faculty of Health and Medical Sciences, Kanagawa Institute of Technology Fac. Health & Med. Sci., Kanagawa Inst. Tech. Lacteals play a critical role in the absorption and transport of dietary lipids into the circulation. We examined the role of signaling for receptor activity-modifying protein 1 (RAMP1), a subunit of CGRP receptor, in lacteal morphology and function in response to a high-fat diet (HFD). RAMP1 deficient (RAMP1^–/–) or wild-type (WT) mice were fed a normal diet or HFD for 8 weeks. RAMP1^–/– mice fed an HFD showed heavier body weights than WT mice fed an HFD, which was associated with high levels of total cholesterol, triglycerides, and glucose. HFD-fed RAMP1^–/– mice had shorter length of lacteals and greater width of lacteals than HFD-fed WT mice. HFD-fed RAMP1^–/– mice had lower gene expression levels of lymphatic endothelial cell markers including VEGFR3, and lymphatic vascular growth factor VEGF-C than HFD-fed WT mice. The concentration of the absorbed lipid tracer in HFD-fed RAMP1^–/– mice was higher than that in HFD-fed WT mice. The zipper-like continuous junctions were predominant in HFD-fed WT mice, while the button-like discontinuous junctions were predominant in HFD-fed RAMP1^–/– mice. These results suggest that deletion of RAMP1 signaling suppressed lacteal growth and VEGF-C/VEGFR3 expression and accelerated the uptake and transport of dietary fats through discontinuous junctions of lacteals, leading to excessive obesity.