The mechanism of anorectic effect from MCH1R antagonism in the peripheral tissue

2012 Fiscal Year Final Research Report

• Project/Area Number: 22500331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Fujita Health University
• Principal Investigator: NAGASAKI Hiroshi 藤田保健衛生大学, 医学部, 准教授 (30420384)
• Project Period (FY): 2010 – 2012
• Keywords: メラニン凝集ホルモン

Research Abstract

We have developed a non-peptide antagonist formelanin-concentrating hormone receptor 1 (MCH1R), TPI1361-17 (TPI). TPI does not crossblood brain barrier, and the intra-peritoneal administration cause prominent anorexiceffect in mice, which suggest MCH system localize in peripheral tissues, as well as incentral nervous systems. Oral glucose load reduced MCH level in circulation. In thediet-induced obese mice, TPI reduced body weight, food intake, and improved insulinresistance. These results suggest that MCH system localize in peripheral tissues and itmay regulate energy homeostasis.

Research Products

• [Journal Article] Lesion of area postrema attenuated hyperphagic responses to glucoprivation, but not transcriptional activation of the neuropeptide Y gene in rats (2012)
  • Author(s): Ozawa Y, Arima H, Banno R, Ito Y, Goto M, Morishita Y, Sugimura Y, Ozaki N, Nagasaki H, Oiso Y
  • Journal Title: Neuroreport Volume: 23(11) Pages: 673-5
  • Peer Reviewed
• [Journal Article] Inflammatory changes in adiposetissue enhance expression of GPR84 (2012)
  • Author(s): Nagasaki H, Kondo T, Fuchigami M,Hashimoto H, Sugimura Y, Ozaki N,Arima H, Ota A, Oiso Y, Hamada Y
  • Journal Title: a medium-chain fatty acid receptor TNFa enhances GPR84 expression inadipocytes FEBS Letters Volume: 586 Pages: 368-372
  • Peer Reviewed
• [Journal Article] Reduction of Insulin SignalingUpregulates Angiopoietin-likeProtein 4 Through Elevated FreeFatty Acids in Diabetic Mice. (2012)
  • Author(s): Mizutani N. Ozaki N, Seino Y, FukamiA, Sakamoto E, Fukuyama T, Sugimura Y,Nagasaki H, Arima H, Oiso Y.
  • Journal Title: Exp Clin Endocrinol Diabetes Volume: 120(03) Pages: 139-144
  • Peer Reviewed
• [Journal Article] Palmitate induces apoptosis inSchwann cells via bothceramide-dependent and independentpathways (2011)
  • Author(s): Suzuki J, Akahane K, Nakamura J, Naruse K, Kamiya H, Himeno T, NakamuraN, Shibata T, Kondo M, Nagasaki H,Fujiya A, Oiso Y, Hamada Y
  • Journal Title: Neuroscience Volume: 176 Pages: 188-198
  • Peer Reviewed
• [Journal Article] Repeated glucodeprivation delayedhyperphagic responses whileactivating neuropeptide Y neuronsin rats (2011)
  • Author(s): Ozawa Y, Arima H, Watanabe M, ShimizuH, Ito Y, Banno R, Sugimura Y, OzakiN, Nagasaki H, Oiso Y
  • Journal Title: Peptides Volume: 32 Pages: 763-769
  • Peer Reviewed
• [Journal Article] Low-serum culture system improvesthe adipogenic ability of visceral adipose tissue-derived stromalcells (2011)
  • Author(s): Nagasaki H, Shang Q, Suzuki T,Hashimoto H, Yoshimura T, Kondo TA,Ozaki T, Maruyama S, Jomori T, Oiso Y,Hamada Y.
  • Journal Title: Cell Biol Int Volume: 35 Pages: 559-568
  • Peer Reviewed
• [Journal Article] 特集摂食制御の分子過程「メラニン凝集ホルモン-MCH」 (2011)
  • Author(s): 長崎 弘
  • Journal Title: 斎藤祐見子生体の科学 Volume: Vol.62 No.1 Pages: p37-43
• [Journal Article] Glucocorticoids increase NPY geneexpression in the arcuate nucleus byinhibiting mTOR signaling in rathypothalamic organotypic cultures. (2010)
  • Author(s): Shimizu H, Arima H, Ozawa Y, WatanabeM, Banno R, Sugimura Y, Ozaki N,Nagasaki H, Oiso Y
  • Journal Title: Peptides Volume: 31 Pages: 145-149
  • Peer Reviewed
• [Journal Article] Acute homeostatic responses toincreased fat consumption in MCH1Rknockout mice (2010)
  • Author(s): Chung S, Wong T, Nagasaki H, Civelli O
  • Journal Title: J Mol Neurosci Volume: 42 Pages: 459-463
  • Peer Reviewed
• [Journal Article] メラニン凝集ホルモン(MCH) (2010)
  • Author(s): 長崎弘
  • Journal Title: 斎藤祐見子広範囲血液・尿化学検査免疫学的検査 (4)日本臨床 Volume: 68巻増刊号7 Pages: 230-233
• [Presentation] MCH1R受容体阻害剤の同定とエネルギー調節研究への応用 (2012)
  • Author(s): 長崎弘
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 20120419-21
• [Presentation] マウスES細胞由来-視床下部培養系における視床下部ニューロンの発生 (2012)
  • Author(s): 長崎弘
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 20120419-21
• [Presentation] 脂肪酸G蛋白結合受容体GPR40に対するチアゾリジン誘導体の作用 (2012)
  • Author(s): 長崎弘
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 20120419-21