Identification and functional analysis of novel hypothalamic peptides

• Project/Area Number: 20591100
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: University of Miyazaki
• Principal Investigator: YAMAGUCHI Hideki University of Miyazaki, 医学部, 講師 (10305097)
• Co-Investigator(Kenkyū-buntansha): TOSHINAI Koji 宮崎大学, 医学部, 講師 (80381101)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 生理活性ペプチド / 摂食調節 / エネルギー代謝調節 / 免疫染色

Research Abstract

We have identified two novel carboxy-terminally amidated peptides, Neuroendocrine regulatory peptide (NERP)-1 and NERP-2. Icv administration of NERP-2 increased food intake in rats. NERP-2 expression localized to the lateral hypothalamus, colocalizing with orexins that activate feeding behavior and arousal. Icv administration of NERP-2 also increased body temperature, oxygen consumption, and locomotor activity in rats. Bioactivities of NERP-2 were abrogated by blunting orexin signaling pathway. NERP-2 plays a role in the control of food intake and energy homeostasis via the orexin pathway.

Research Products

• [Journal Article] Localization of neuroendocrine regulatory peptide-1 and -2 in human tissues (2010)
  • Author(s): Matsuo T, Yamaguchi H, Kageyamma H, Sasaki K, Shioda S, Minamino N, Nakazato M.
  • Journal Title: Regul Pept 163 Pages: 43-48
  • Peer Reviewed
• [Journal Article] Distribution of neuroendocrine regulatory peptide-1 and -2, and proteolytic processing of their precursor VGF protein in the rat. (2010)
  • Author(s): Mishiro-Sato E, Sasaki K, Matsuo T, Kageyama H, Yamaguchi H, Date Y, Matsubara M, Ishizu T, Yoshizawa-Kumagaye K, Satomi Y, Takao T, Shioda S, Nakazato M, Minamino N.
  • Journal Title: J Neurochem. 114 Pages: 1097-1106
  • Peer Reviewed
• [Journal Article] Neuroendocrine regulatory peptide-2 regulates feeding behavior via the orexin system in the hypothalamus. (2010)
  • Author(s): Toshinai K, Yamaguchi H, Kageyama H, Matsuo T, Koshinaka K, Sasaki K, Shioda S, Minamino N, Nakazato M
  • Journal Title: Am J Physiol Endocrinol Metab. 299
  • Peer Reviewed
• [Journal Article] Localization of neuroendocrine regulatory peptide-1 and -2 in human tissues. (2010)
  • Author(s): Matsuo T, Yamaguchi H, Kageyama H, Sasaki K, Shioda S, Minamino N, Nakazato M.
  • Journal Title: Regul Pept Volume: 163 Pages: 43-48
  • Peer Reviewed
• [Journal Article] Neuropeptide W : an anorectic peptide regulated by leptin and metabolic state. (2010)
  • Author(s): Date Y, Mondal MS, Kageyama H, Ghamari-Langroudi M, Takenoya F, Yamaguchi H, Shimomura Y, Mori M, Murakami N, Shioda S, Cone RD, Nakazato M.
  • Journal Title: Endocrinology Volume: 151 Pages: 2200-2210
  • Peer Reviewed
• [Journal Article] Distribution of neuroendocrine regulatory peptide-1 and -2, and proteolytic processing of their precursor VGF protein in the rat. (2010)
  • Author(s): Mishiro-Sato E, Sasaki K, Matsuo T, Kageyama H, Yamaguchi H, Date Y, Matsubara M, Ishizu T, Yoshizawa-Kumagaye K, Satomi Y, Takao T, Shioda S., Nakazato M., Minamino N.
  • Journal Title: J Neurochem. Volume: 114 Pages: 1097-1106
  • Peer Reviewed
• [Journal Article] Neuroendocrine regulatory peptide-2 regulates feeding behavior via the orexin system in the hypothalamus. (2010)
  • Author(s): Toshinai K, Yamaguchi H, Kageyama H, Matsuo T, Koshinaka K, Sasaki K, Shioda S, Minamino N, Nakazato M
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 299
  • Peer Reviewed
• [Journal Article] A novel nonsense mutation in the DMP1 gene in a Japanese family with autosomal recessive hypophosphatemic rickets (2010)
  • Author(s): Koshida R, Yamaguchi H, Yamasaki K, Tsuchimochi W, Yonekawa T, Nakazato M
  • Journal Title: J Bone Miner Metab. (Epub ahead of print)
  • NAID: 10027684151
  • Peer Reviewed
• [Journal Article] Myasthenia gravis complicated with primary aldosteronism hypokalemic myopathy (2009)
  • Author(s): Yamashita S, Tsuchimochi W, Yonekawa T, Yamachi H, Kyoraku I, Shiomi K, Nakazato M
  • Journal Title: Intern Med 48 Pages: 1465-1459
  • Peer Reviewed
• [Journal Article] 新規視床下部ペプチドNERPによる水・電解質代謝調節 (2008)
  • Author(s): 山口秀樹、中里雅光
  • Journal Title: 医学のあゆみ Vol 227 Pages: 953-957
• [Journal Article] The role of PYY in feeding regulation. (2008)
  • Author(s): Ueno H, Yamaguchi H, Mizuta M, Nakazato M.
  • Journal Title: Regul Pept 145 Pages: 12-16
  • Peer Reviewed
• [Journal Article] Ontogeny of a new enteric peptide, neuropeptide W (NPW), in the developing rat stomach. (2008)
  • Author(s): Mondal MS, Yamaguchi H, Date Y, Tsuruta T, Shimbara T, Toshinai K, Shimomura Y, Mori M, Nakazato M.
  • Journal Title: Regul Pept, 145 : 141-146 (2008) 145 Pages: 141-146
  • Peer Reviewed
• [Journal Article] A hypothalamic peptide, neuroendocrine regulatory peptide-2, modulates the orexin system.
  • Author(s): Toshinai K, Yamaguchi H, Kageyama H, Matsuo T, Koshinaka K, Sasaki K, Shioda S, inamino N, Nakazato M
  • Journal Title: Endocrinology, in press
  • Peer Reviewed
• [Presentation] Neuroendocrine regulatory peptides (NERPs) suppress presynaptic glutamatergic neurons and activate GABAergic interneurons to inhibit vasopressin secretion (2010)
  • Author(s): 山口秀樹
  • Organizer: 14th International Congress of Endocrinology (ICE2010)
  • Place of Presentation: 京都
  • Year and Date: 2010-03-30
• [Presentation] Localization of novel neuroendocrine regulatory peptides, NERP-1 and-2, in human brain and pancreas (2010)
  • Author(s): 松尾崇
  • Organizer: 14th International Congress of Endocrinology (ICE2010)
  • Place of Presentation: 京都
  • Year and Date: 2010-03-30
• [Presentation] Endogenous molecular forms of neurorndocrine regulatory peptides and their proteolytic processing from VGF protein in the rat (2010)
  • Author(s): 三城恵美
  • Organizer: 14th International Congress of Endocrinology (ICE2010)
  • Place of Presentation: 京都
  • Year and Date: 2010-03-29
• [Presentation] 新規生理活性ペプチドNERPのヒト脳および膵臓での局在 (2010)
  • Author(s): 松尾崇
  • Organizer: 第83回日本内分泌学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-25
• [Presentation] 新規生理活性ペプチドNERPのヒト神経内分泌組織での局在 (2010)
  • Author(s): 松尾崇、山口秀樹、影山晴秋、佐々木一樹、塩田清二、南野直人、中里雅光
  • Organizer: 第37回日本神経内分泌学会
  • Place of Presentation: 京都
• [Presentation] 視床下部ペプチドNERPのAVP分泌抑制機序の解析 (2009)
  • Author(s): 山口秀樹
  • Organizer: 第82回日本内分泌学会総会
  • Place of Presentation: 群馬
  • Year and Date: 2009-04-25
• [Presentation] 視床下部ペプチドNERPsはシナプス前グルタミン酸放出とAVP分泌を抑制する (2009)
  • Author(s): 斉藤健, 山口秀樹, 佐々木一樹, 南野直人, 上田陽一, 中里雅光
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬県民会館
• [Presentation] 手術を要したプロラクチノーマの臨床像の検討 (2009)
  • Author(s): 米川忠人, 山口秀樹, 土持若葉, 中里雅光
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬県民会館
• [Presentation] Peptidomic identificationand biological validation of neuroendocrine regulatory peptide-1 and-2 (2008)
  • Author(s): 山口秀樹
  • Organizer: 米国内分泌学会
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2008-06-16
• [Presentation] Characterization and localization of novel neuroendocrine regulatory peptides, NERP-1 and-2, in the human plasma and the hypothalamus (2008)
  • Author(s): 松尾崇
  • Organizer: 米国内分泌学会
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2008-06-16
• [Presentation] 新規視床下部ペプチドNERPの機能解析 (2008)
  • Author(s): 山口秀樹
  • Organizer: 第81回日本内分泌学会総会
  • Place of Presentation: 青森
  • Year and Date: 2008-05-16
• [Presentation] 新規生理活性ペプチドNERPのヒトにおける血中濃度と生理学的変動の検討 (2008)
  • Author(s): 山口秀樹
  • Organizer: 第81回日本内分泌学会総会
  • Place of Presentation: 青森
  • Year and Date: 2008-05-16
• [Presentation] 新規生理活性ペプチドNERPの機能解析 (2008)
  • Author(s): 山口秀樹, 佐々木一樹, 里見佳典, 影山晴秋, 伊達 紫, 十枝内厚次, Muhtashan S. Mondal, 新原琢也. 松尾 崇, 塩田清二, 高尾敏文, 南野直人, 中里雅光
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森