The study of anti-obesity effect by recovery of endogenous oxytocin secretion and its clinical implication

• Project/Area Number: 18K08483
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Maejima Yuko 福島県立医科大学, 医学部, 准教授 (40438669)
• Co-Investigator(Kenkyū-buntansha): 下村 健寿 福島県立医科大学, 医学部, 教授 (90636226)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: オキシトシン / 肥満 / GLP-1 / 食欲 / マウス / メタボリックシンドローム

Outline of Final Research Achievements

It has been reported that neuropeptide oxytocin (Oxt) has anti-obesity effects. On the other hand, GLP-1 has already been approved as anti-obesity drug in US and Europe. The present study examined the effects of peripheral co-administration of Oxt and GLP-1 on the feeding and body weight in high fat diet induced obese mice. Co-administration of low dose Oxt and GLP-1 enhanced anti-obesity effects than single administration of Oxt and GLP-1, respectively. Co-administration of Oxt and GLP-1 stimulate neuronal activity in paraventricular nucleus (PVN), which is important for the anorexigenic effects. Enhanced anti-obesity effects induced by Oxt and GLP-1 may mediate neuronal activity in the PVN.

Academic Significance and Societal Importance of the Research Achievements

本研究は抗肥満効果のあることが知られている２種類のホルモン、オキシトシンとGLP-1の共投与が肥満マウスを効率よく体重減少させるかを調べ、それぞれ単独よりも抗肥満効果が増強されることを明らかにした。近年、複数の成分を組み合わせることで、単剤よりも高い効果や安全性という観点から「合剤」が注目されているが、本研究では低用量オキシトシンとGLP-1を組み合わせることでより高い食欲抑制・抗肥満効果を明らかにした。現在安全な抗肥満薬が存在しない中、本研究で明らかになったオキシトシンとGLP-1の組み合わせにより高い抗肥満効果が得られることは、臨床応用という観点からも非常に有意義な成果であると考えられる。

Research Products

• [Journal Article] Structure based analysis of KATP channel with a DEND syndrome mutation in murine skeletal muscle (2021)
  • Author(s): Horita Shoichiro、Ono Tomoyuki、Gonzalez-Resines Saul、Ono Yuko、Yamachi Megumi、Zhao Songji、Domene Carmen、Maejima Yuko、Shimomura Kenju
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 6668-6668
  • DOI: 10.1038/s41598-021-86121-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of organ glucose metabolism by 18F-FDG accumulation with insulin loading in aged mice compared with young normal mice (2021)
  • Author(s): Zhao Jingmin、Tan Chengbo、Imai Ryota、Ukon Naoyuki、Shimoyama Saki、Maejima Yuko、Omiya Yuji、Takahashi Kazuhiro、Ito Hiroshi、Nan Guangxian、Zhao Songji、Shimomura Kenju
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 7421-7421
  • DOI: 10.1038/s41598-021-86825-8
  • Peer Reviewed / Open Access
• [Journal Article] Oral oxytocin delivery with proton pump inhibitor pretreatment decreases food intake (2020)
  • Author(s): Maejima Yuko、Horita Shoichiro、Otsuka Ayano、Hidema Shizu、Nishimori Katsuhiko、Shimomura Kenju
  • Journal Title: Peptides Volume: 128 Pages: 170312-170312
  • DOI: 10.1016/j.peptides.2020.170312
  • Peer Reviewed
• [Journal Article] Goshajinkigan, a Traditional Japanese Medicine, Suppresses Voltage-Gated Sodium Channel Nav1.4 Currents in C2C12 Cells (2020)
  • Author(s): Imai Ryota、Horita Shoichiro、Ono Yuko、Hagihara Keisuke、Shimizu Masaru、Maejima Yuko、Shimomura Kenju
  • Journal Title: BioResearch Open Access Volume: 9 Issue: 1 Pages: 116-120
  • DOI: 10.1089/biores.2019.0034
  • Peer Reviewed / Open Access
• [Journal Article] Early life high-fat diet exposure evokes normal weight obesity (2020)
  • Author(s): Maejima Yuko、Yokota Shoko、Horita Shoichiro、Shimomura Kenju
  • Journal Title: Nutrition & Metabolism Volume: 17 Issue: 1 Pages: 2020-2020
  • DOI: 10.1186/s12986-020-00464-w
  • Peer Reviewed / Open Access
• [Journal Article] Gs/Gq signaling switch in β cells defines incretin effectiveness in diabetes (2020)
  • Author(s): Oduori Okechi S.、Murao Naoya、Shimomura Kenju、Takahashi Harumi、Zhang Quan、Dou Haiqiang、Sakai Shihomi、Minami Kohtaro、Chanclon Belen、Guida Claudia、Kothegala Lakshmi、Tol? Johan、Maejima Yuko、Yokoi Norihide、Minami Yasuhiro、Miki Takashi、Rorsman Patrik、Seino Susumu
  • Journal Title: Journal of Clinical Investigation Volume: 130 Issue: 12 Pages: 6639-6655
  • DOI: 10.1172/jci140046
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Detection of NUCB2/nesfatin-1 in cerebrospinal fluid of multiple sclerosis patients (2020)
  • Author(s): Shimizu Masaru、Manome Taizo、Kumami Masumi、Matsumura Kouzou、Kanai Kazuaki、Shimomura Kenju、Maejima Yuko
  • Journal Title: Aging Volume: 12 Issue: 23 Pages: 24134-24140
  • DOI: 10.18632/aging.202287
  • Peer Reviewed / Open Access
• [Journal Article] Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models (2020)
  • Author(s): Horiai Machi、Otsuka Ayano、Hidema Shizu、Hiraoka Yuichi、Hayashi Ryotaro、Miyazaki Shinji、Furuse Tamio、Mizukami Hiroaki、Teruyama Ryoichi、Tamura Masaru、Bito Haruhiko、Maejima Yuko、Shimomura Kenju、Nishimori Katsuhiko
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 22173-22173
  • DOI: 10.1038/s41598-020-79109-0
  • Peer Reviewed / Open Access
• [Book] 最強の医師団が教える 長生きできる方法 (2020)
  • Author(s): 坂本昌也、頴川晋、北原雅樹、齋田良知、繁田雅弘、下村健寿、炭山和毅、鳥海弥寿雄、前島裕子、三澤健之
  • Total Pages: 216
  • Publisher: アスコム
  • ISBN: 9784776211006