Regulation of cytoskeleton and energy metabolism in adipocytes by adrenomedullin-RAMP2 system

• Project/Area Number: 16K08545
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Shinshu University
• Principal Investigator: KAMIYOSHI Akiko 信州大学, 学術研究院医学系, 助教 (10397309)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アドレノメデュリン / 脂肪細胞

Outline of Final Research Achievements

Adrenomedullin (AM) is a vasodilatory peptide, which possess various bioactivities. AM and receptor activity-modifying protein 2 (RAMP2) are highly expressed in adipose tissues. In this study, to clarify the regulation of cytoskeleton and energy metabolism in adipocytes by AM-RAMP2 system, we analyzed adipocyte-specific RAMP2 knockout mice. We showed that AM-RAMP2 system regulates cytoskeleton of inguinal white adipose tissue and brown adipose tissue, and participates in adipocyte differentiation and energy metabolism.

Academic Significance and Societal Importance of the Research Achievements

AMはペプチドで血中半減期が短いため、それ自体を慢性疾患の治療薬として利用することは難しい。そこで、AMの受容体側に着目し、その受容体活性調節タンパクであるRAMP2を標的とした治療法の開発を検討している。RAMP2は1回膜貫通型タンパクであり、比較的単純な構造のため治療標的分子となる可能性が高いと考えられ、本研究の成果により、RAMP2を標的としたメタボリックシンドロームの治療法開発に展開することが期待される。

Research Products

• [Journal Article] Development of a novel model of central retinal vascular occlusion and the therapeutic potential of the adrenomedullin-RAMP2 system. (2019)
  • Author(s): Hirabayashi K, Tanaka M, Imai A, Toriyama Y, Iesato Y, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Tanaka M, Dai K, Cui N, Wei Y, Nakamura K, Iida S, Matsui S, Yamauchi A, Murata T, Shindo T.
  • Journal Title: Am J Pathol. Volume: 189 Issue: 2 Pages: 449-466
  • DOI: 10.1016/j.ajpath.2018.10.021
  • Peer Reviewed
• [Journal Article] Development of a novel model of central retinal vascular occlusion and the therapeutic potential of the adrenomedullin-RAMP2 system. (2019)
  • Author(s): Hirabayashi K, Tanaka M, Imai A, Toriyama Y, Iesato Y, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Tanaka M, Dai K, Cui N, Wei Y, Nakamura K, Iida S, Matsui S, Yamauchi A, Murata T, Shindo T.
  • Journal Title: Am J Pathol. Volume: 189 Pages: 449-466
  • DOI: 10.1016/j.peptides.2018.10.006
  • Peer Reviewed
• [Journal Article] Regulation of cardiovascular development and homeostasis by the adrenomedullin-RAMP system (2019)
  • Author(s): Shindo T, Tanaka M, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Yamauchi A, Sakurai T.
  • Journal Title: Peptides. Volume: 111 Pages: 55-61
  • DOI: 10.1016/j.peptides.2018.04.004
  • Peer Reviewed
• [Journal Article] Adrenomedullin Suppresses Vascular Endothelial Growth Factor-Induced Vascular Hyperpermeability and Inflammation in Retinopathy. (2017)
  • Author(s): Imai A, Toriyama Y, Iesato Y, Hirabayasi K, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Tanaka M, Liu T, Xian X, Zhai L, Dai K, Tanimura K, Liu T, Cui N, Yamauchi A, Murata T, Shindo T
  • Journal Title: American journal of Pathology Volume: 187(5) Issue: 5 Pages: 999-1015
  • DOI: 10.1016/j.ajpath.2017.01.014
  • Peer Reviewed
• [Journal Article] Placental extract ameliorates non-alcoholic steatohepatitis (NASH) by exerting protective effects on endothelial cells (2017)
  • Author(s): Yamauchi A, Kamiyoshi A, Koyama T, Iinuma N, Yamaguchi S, Miyazaki H, Hirano E, Kaku T, Shindo T.
  • Journal Title: Heliyon Volume: 3(9) Issue: 9 Pages: e00416-e00416
  • DOI: 10.1016/j.heliyon.2017.e00416
  • Peer Reviewed
• [Journal Article] Endogenous calcitonin gene-related peptide regulates lipid metabolism and energy homeostasis in male mice (2017)
  • Author(s): Liu T, Tanaka M, et al.
  • Journal Title: Endocrinology Volume: 158 Issue: 5 Pages: 1194-1206
  • DOI: 10.1210/en.2016-1510
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Vasoprotective activities of the adrenomedullin-RAMP2 system in endothelial cells (2017)
  • Author(s): Xian X, Tanaka M, et al.
  • Journal Title: Endocrinology Volume: 158 Issue: 5 Pages: 1359-1372
  • DOI: 10.1210/en.2016-1531
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The endothelial adrenomedullin-RAMP2 system regulates vascular integrity and suppresses tumour metastasis (2016)
  • Author(s): Tanaka M, et al.
  • Journal Title: Cardiovascular Research Volume: 111 Issue: 4 Pages: 398-409
  • DOI: 10.1093/cvr/cvw166
  • Peer Reviewed
• [Presentation] RAMP3 Deficiency Enhances Postmenopausal Obesity and Metabolic Disorders (2019)
  • Author(s): 神吉昭子、桜井敬之、新藤優佳、河手久香、田中愛、平林一貴、戴昆、崔南奇、Yangxuan Wei、田中正明、松井周平、中村啓成、飯田紫帆、山内啓弘、新藤隆行
  • Organizer: 第83回日本循環器学会
• [Presentation] アドレノメデュリン-RAMP2系による脂肪細胞の細胞骨格とエネルギー代謝制御機構 (2018)
  • Author(s): 神吉昭子、桜井敬之、河手久香、新藤優佳、田中愛、平林一貴、戴昆、崔南奇、田中正明、Wei Yangxuan、劉騰、冨山遥、中村啓成、飯田紫帆、松井周平、山内啓弘、新藤隆行
  • Organizer: 第39回日本肥満学会
• [Presentation] Regulation of Cytoskeleton and Energy Metabolism of Adipocytes by Adrenomedullin-RAMP2 System (2018)
  • Author(s): Akiko Kamiyoshi, Takayuki Sakurai, Yuka Ichikawa-Shindo, Hisaka Kawate, Megumu Tanaka, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Nanqi Cui, Yangxuan Wei, Masaaki Tanaka, Keiya Tanimura, Teng Liu, Haruka Tomiyama, Shuhei Matsui, Akihiro Yamauchi, Takayuki Shindo.
  • Organizer: 第82回日本循環器学会
• [Presentation] Endogenous calcitonin gene-related peptide regulates lipid metabolism and energy homeostasis in vivo (2017)
  • Author(s): 劉甜、神吉昭子、桜井敬之、新藤優佳、河手久香、田中愛、羨鮮、今井章、Liuyu Zhai、平林一貴、戴昆、谷村圭哉、劉騰、崔南奇、Yangxuan Wei、五十嵐恭子、山内啓弘、新藤隆行
  • Organizer: 第81回日本循環器学会
  • Place of Presentation: 石川県立音楽堂（石川県金沢市）
  • Year and Date: 2017-03-17
• [Presentation] アドレノメデュリン-RAMP2系による脂肪細胞の細胞骨格およびエネルギー代謝制御機構 (2017)
  • Author(s): 神吉昭子、桜井敬之、新藤優佳、河手久香、田中愛、Liuyu Zhai、平林一貴、田中正明、劉騰、新藤隆行
  • Organizer: 第21回日本心血管内分泌代謝学会
• [Presentation] アドレノメデュリン-RAMP2系は褐色脂肪細胞とベージュ脂肪細胞の分化を制御する (2017)
  • Author(s): 神吉昭子、桜井敬之、河手久香、新藤優佳、田中愛、羨鮮、Liuyu Zhai、平林一貴、戴昆、崔南奇、田中正明、谷村圭哉、劉騰、冨山 遥、Yangxuan Wei、山内啓弘、新藤隆行
  • Organizer: 第38回日本肥満学会
• [Presentation] A multiple-gene modified mouse production by using maternal Cas9 in the zygotes prepared from transgenic mice systemically expressing Cas9 (2016)
  • Author(s): Takayuki Sakurai, Akiko Kamiyoshi, Hisaka Kawate, Chie Mori, Satoshi Watanabe, Masahiro Sato, Takayuki Shindo
  • Organizer: 第1回日本ゲノム編集学会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2016-09-06
• [Presentation] アドレノメデュリン-RAMP2系は褐色脂肪細胞の細胞分化とエネルギー代謝を制御する (2016)
  • Author(s): 神吉昭子、桜井敬之、新藤優佳、河手久香、田中愛、劉甜、羨鮮、今井章、Zhai Liuyu、平林一貴、大和慎治、戴昆、崔南奇、劉騰、五十嵐恭子、山内啓弘、新藤隆行
  • Organizer: 第89回日本内分泌学会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-21
• [Presentation] カルシトニン遺伝子関連ペプチド（CGRP）は、白色脂肪組織の脂肪分解を抑制する (2016)
  • Author(s): 劉甜、桜井敬之、神吉昭子、新藤優佳、河手久香、田中愛、羨鮮、今井章、Zhai Liuyu、平林一貴、大和慎治、戴昆、崔南奇、劉騰、五十嵐恭子、山内啓弘、新藤隆行
  • Organizer: 第89回日本内分泌学会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-21