Homeostatic regulation of autonomous nerves system by ghrelin

• Project/Area Number: 21390287
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kurume University
• Principal Investigator: KOJIMA Masayasu 久留米大学, 分子生命科学研究所, 教授 (20202062)
• Co-Investigator(Renkei-kenkyūsha): SATO Takahiro 久留米大学, 分子生命科学研究所, 准教授 (50368883) ; IDA Takanori 宮崎大学, IR推進機構, IRO特任助教 (00381088)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2009: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: グレリン / 自律神経 / 体温調節 / トーパー / 脂肪酸転移酵素 / ノックアウトマウス / 褐色脂肪組織 / 日内冬眠 / 血圧 / 体温 / 消化管運動

Research Abstract

Ghrelin decreases body temperature. In a hot condition, ghrelin production in stomach is stimulated and plasma ghrelin concentration is increased in mice. In addition, ghrelin KO mice shows high mortality rate in a hot condition, suggesting that these mice lack normal regulatory mechanism of body temperature. Small animals like mice show torpor(daily hibernation) induction after long term food deprivation. In torpor state, they show low body temperature and decrease of activity. However, ghrelin KO mice do not show torpor induction and suppression of energy. Thus, ghrelin is a survival hormone necessary to suppress metabolism and activity.

Research Products

• [Journal Article] Increased production of active ghrelin is relevant to hyperphagia in nonobese spontaneously diabetic Torii rats (2012)
  • Author(s): Mifune H, Nishi Y, Tajiri Y, Masuyama T, Hosoda H, Kangawa K, Kojima M
  • Journal Title: Metabolism Volume: 61(4) Pages: 491-5
  • Peer Reviewed
• [Journal Article] Disrupted Regulation of Ghrelin Production Under Antihypertensive Treatment in Spontaneously Hypertensive Rats (2012)
  • Author(s): Hamada N, Nishi Y, Tajiri Y, Setoyama K, Kamimura R, Miyahara K, Nuruki N, Hosoda H, Kangawa K, Kojima M, Mifune H
  • Journal Title: Circ J. Volume: (in press)
  • NAID: 10030316253
  • Peer Reviewed
• [Journal Article] Effects of calcium salts of long-chain fatty acids and rumen-protected methionine on plasma concentrations of ghrelin, glucagon-like peptide-1(7 to 36) amide and pancreatic hormones in lactating cows (2012)
  • Author(s): Fukumori R, Sugino T, Shingu H, Moriya N, Hasegawa Y, Kojima M, Kangawa K, Obitsu T, Kushibiki S, Taniguchi K
  • Journal Title: Domest Anim Endocrinol Volume: 42(2) Pages: 74-82
  • NAID: 120005308234
  • Peer Reviewed
• [Journal Article] Structure, regulation and function of ghrelin (2012)
  • Author(s): Sato T, Nakamura Y, Shiimura Y, Ohgusu H, Kangawa K, Kojima M
  • Journal Title: J Biochem Volume: 151(2) Pages: 119-28
  • NAID: 10031166050
  • Peer Reviewed
• [Journal Article] Effects of calcium salts of long-chain fatty acids and rumen-protected methionine on plasma concentrations of ghrelin, glucagon-like peptide-1 (7 to 36) amide and pancreatic hormones in lactating cows (2012)
  • Author(s): Fukumori R, Sugino T, Shingu H, Moriya N, Hasegawa Y, Kojima M, Kangawa K, Obitsu T, Kushibiki S, Taniguchi K
  • Journal Title: Domest Anim Endocrinol Volume: 42 Pages: 74-82
  • NAID: 120005308234
  • Peer Reviewed
• [Journal Article] The discovery of ghrelin : with a little luck and great passion (2011)
  • Author(s): Kojima M, Kangawa K
  • Journal Title: Preface. Peptides Volume: 32(11) Pages: 2153-4
• [Journal Article] Structures and molecular forms of the ghrelin-family peptides (2011)
  • Author(s): Nishi Y, Yoh J, Hiejima H, Kojima M
  • Journal Title: Peptides Volume: 32(11) Pages: 2175-82
• [Journal Article] Ghrelin levels are reduced in Rett syndrome patients with eating difficulties (2011)
  • Author(s): Hara M, Nishi Y, Yamashita Y, Yoh J, Takahashi S, Nagamitsu S, Kakuma T, Hosoda H, Kangawa K, Kojima M, Matsuishi T
  • Journal Title: Int J Dev Neurosci Volume: 29(8) Pages: 899-902
  • Peer Reviewed
• [Journal Article] Effects of amino acids infused into the vein on ghrelin-induced GH, insulin and glucagon secretion in lactating cows (2011)
  • Author(s): Fukumori R, Yokotani A, Sugino T, Itoh F, Kushibiki S, Shingu H, Moriya N, Hasegawa Y, Kojima M, Kangawa K, Obitsu T, Taniguchi K
  • Journal Title: Anim Sci J. Volume: 82(2) Pages: 267-73
  • NAID: 10030376357
  • Peer Reviewed
• [Journal Article] Plasma ghrelin concentration is decreased by short chain fatty acids in wethers (2011)
  • Author(s): Fukumori R, Sugino T, Hasegawa Y, Kojima M, Kangawa K, Obitsu T, Taniguchi K
  • Journal Title: Domest Anim Endocrinol Volume: 41(1) Pages: 50-5
  • Peer Reviewed
• [Journal Article] Plasma levels of n-decanoyl ghrelin, another acyl-and active-form of ghrelin, in human subjects and the effect of glucose-or meal-ingestion on its dynamics (2011)
  • Author(s): Yoh J, Nishi Y, Hosoda H, Tajiri Y, Yamada K, Yanase T, Doi R, Yonemoto K, Kangawa K, Kojima M, Tanaka E, Kusukawa J
  • Journal Title: Regul Pept Volume: 167(1) Pages: 140-8
  • Peer Reviewed
• [Journal Article] Factors associated with plasma ghrelin level in Japanese general population (2011)
  • Author(s): Nanjo Y, Adachi H, Hirai Y, Enomoto M, Fukami A, Otsuka M, Yoshikawa K, Yokoi K, Ogata K, Tsukagawa E, Kasahara A, Murayama K, Yasukawa H, Kojima M, Imaizumi T
  • Journal Title: Clin Endocrinol(Oxf) Volume: 74(4) Pages: 453-8
  • Peer Reviewed
• [Journal Article] Continuous antagonism of the ghrelin receptor results in early induction of salt-sensitive hypertension (2011)
  • Author(s): Sato T, Nakashima Y, Nakamura Y, Ida T, Kojima M
  • Journal Title: J Mol Neurosci Volume: 43(2) Pages: 193-9
  • Peer Reviewed
• [Journal Article] Effects of amino acids infused into the vein on ghrelin-induced GH, insulin and glucagon secretion in lactating cows (2011)
  • Author(s): Fukumori R, Yokotani A, Sugino T, Itoh F, Kushibiki S, Shingu H, Moriya N, Hasegawa Y, Kojima M, Kangawa K, Obitsu T, Taniguchi K
  • Journal Title: Anim Sci J Volume: 82 Pages: 267-273
  • NAID: 10030376357
  • Peer Reviewed
• [Journal Article] Plasma ghrelin concentration is decreased by short chainfatty acids in wethers (2011)
  • Author(s): Fukumori R, Sugino T, Hasegawa Y, Kojima M, Kangawa K, Obitsu T, Taniguchi K
  • Journal Title: Domest Anim Endocrinol Volume: 41 Pages: 50-55
  • Peer Reviewed
• [Journal Article] Plasma levels of n-decanoyl ghrelin, another acyl- and active-form of ghrelin, in human subjects and the effect of glucose or meal-ingestion on its dynamics (2011)
  • Author(s): Yoh J, Nishi Y, Hosoda H, Tajiri Y, Yamada K, Yanase T, Doi R, Yonemoto K, Kangawa K, Kojima M, Tanaka E, Kusukawa J
  • Journal Title: Regul Pept Volume: 167 Pages: 140-148
  • Peer Reviewed
• [Journal Article] Factors associated with plasma ghrelin level in Japanese general population (2011)
  • Author(s): Nanjo Y, Adachi H, Hirai Y, Enomoto M, Fukami A, Otsuka M, Yoshikawa K, Yokoi K, Ogata K, Tsukagawa E, Kasahara A, Murayama K, Yasukawa H, Kojima M, Imaizumi T
  • Journal Title: Clin Endocrinol (Oxf) Volume: 74 Pages: 453-458
  • Peer Reviewed
• [Journal Article] Ghrelin : more than endogenous growth hormone secretagogue (2010)
  • Author(s): Kojima M, Kangawa K
  • Journal Title: Ann N Y Acad Sci Volume: 1200 Pages: 140-8
• [Journal Article] Effects of glucose and amino acids on ghrelin secretion in sheep (2010)
  • Author(s): Sugino T, Kawakita Y, Fukumori R, Hasegawa Y, Kojima M, Kangawa K, Obitsu T, Taniguchi K
  • Journal Title: Anim Sci J. Volume: 81(2) Pages: 199-204
  • NAID: 10030374078
  • Peer Reviewed
• [Journal Article] Purification and characterization of caprine ghrelin and its effect on growth hormone release (2010)
  • Author(s): Ida T, Miyazato M, Lin XZ, Kaiya H, Sato T, Nakahara K, Murakami N, Kangawa K, Kojima M.
  • Journal Title: J Mol Neurosci Volume: 42(1) Pages: 99-105
  • Peer Reviewed
• [Journal Article] Dynamics of placental ghrelin production and its receptor expression in a Dahl salt-sensitive rat model of intrauterine growth restriction (2010)
  • Author(s): Nonoshita A, Nishi Y, Takushima S, Oshima M, Hosoda H, Kangawa K, Kojima M, Mifune H, Tanaka E, Hori D, Kamura T
  • Journal Title: Placenta Volume: 31(5) Pages: 358-64
  • Peer Reviewed
• [Journal Article] Changes in blood pancreatic polypeptide and ghrelin concentrations in response to feeding in sheep (2010)
  • Author(s): Takahashi H, Kurose Y, Suzuki Y, Kojima M, Yamaguchi T, Yoshida Y, Azuma Y, Sugino T, Kojima M, Kangawa K, Hasegawa Y, Kobayashi S
  • Journal Title: J Anim Sci Volume: 88(6) Pages: 2103-7
  • Peer Reviewed
• [Journal Article] A postweaning reduction in circulating ghrelin temporarily alters growth hormone(GH) responsiveness to GH-releasing hormone in male mice but does not affect somatic growth (2010)
  • Author(s): Ariyasu H, Iwakura H, Yamada G, Kanamoto N, Bando M, Kohno K, Sato T, Kojima M, Nakao K, Kangawa K, Akamizu T
  • Journal Title: Endocrinology Volume: 151(4) Pages: 1743-50
  • NAID: 120002949719
  • Peer Reviewed
• [Journal Article] Ghrelin : from gene to physiological function (2010)
  • Author(s): Kojima M, Kangawa K
  • Journal Title: Results Probl Cell Differ Volume: 50 Pages: 185-205
• [Journal Article] Continuous antagonism of the ghrelin receptor results in early ind action of salt-sensitive hypertension. (2010)
  • Author(s): T.Sato, Y.Nakashima, Y.Nakamura, T.Ida, M.Kojima.
  • Journal Title: J Mol Neurosci. Volume: 43 Pages: 193-199
  • Peer Reviewed
• [Journal Article] Dynamics of placental ghrelin production and its receptor expression in a Dahl salt-sensitive rat model of intrauterine growth restriction. (2010)
  • Author(s): A.Nonoshita, Y.Nishi, S.Takushima, M.Oshima, H.Hosoda, K.Kangawa, Kojima M, H.Mifune, E.Tanaka, D.Hori, T.Kamura.
  • Journal Title: Placenta Volume: 31 Pages: 358-364
  • Peer Reviewed
• [Journal Article] From Gene to Physiological Function. (2010)
  • Author(s): M.Kojima, K.Kangawa.
  • Journal Title: Results Probl Cell Differ. Volume: 50 Pages: 185-205
  • Peer Reviewed
• [Journal Article] Production of n-octanoyl-modified ghrelin in cultured cells requires prohormone processing protease and ghrelin O-acyltransferase, as well as n-octanoic acid (2009)
  • Author(s): Takahashi T, Ida T, Sato T, Nakashima Y, Nakamura Y, Tsuji A, Kojima M
  • Journal Title: J Biochem Volume: 146(5) Pages: 675-82
  • NAID: 10026304614
  • Peer Reviewed
• [Journal Article] Ghrelin O-acyltransferase(GOAT) has a preference for n-hexanoyl-CoA over n-octanoyl-CoA as an acyl donor (2009)
  • Author(s): Ohgusu H, Shirouzu K, Nakamura Y, Nakashima Y, Ida T, Sato T, Kojima M
  • Journal Title: Biochem Biophys Res Commun Volume: 386(1) Pages: 153-8
• [Journal Article] The role of ghrelin and ghrelin-receptor gene variants and promoter activity in type 2 diabetes (2009)
  • Author(s): Garcia EA, King P, Sidhu K, Ohgusu H, Walley A, Lecoeur C, Gueorguiev M, Khalaf S, Davies D, Grossman AB, Kojima M, Petersenn S, Froguel P, Korbonits M
  • Journal Title: Eur J Endocrinol Volume: 161(2) Pages: 307-15
  • Peer Reviewed
• [Journal Article] Regional distribution and the dynamics of n-decanoyl ghrelin, another acyl-form of ghrelin, upon fasting in rodents (2009)
  • Author(s): Hiejima H, Nishi Y, Hosoda H, Yoh J, Mifune H, Satou M, Sugimoto H, Chiba S, Kawahara Y, Tanaka E, Yoshimatsu H, Uchimura N, Kangawa K, Kojima M
  • Journal Title: Regul Pept Volume: 156(1-3) Pages: 47-56
  • Peer Reviewed
• [Journal Article] Production of n-octanoyl-modified ghrelin in cultured cells requires prohormone processing protease and ghrelin O-acyltransferase, as well as n-octanoic acid (2009)
  • Author(s): Takahashi T, Ida T, Sato T, Nakashima Y, Nakamura Y, Tsuji A, Kojima M.
  • Journal Title: J Biochem. 146 Pages: 675-682
  • NAID: 10026304614
  • Peer Reviewed
• [Journal Article] Ghrelin O-acyltransferase(GOAT)has a preference for n-hexanoyl-CoA over n-octanoyl-CoA as an acyl donor (2009)
  • Author(s): Ohgusu H, Shirouzu K, Nakamura Y, Nakashima Y, Ida T, Sato T, Kojima M.
  • Journal Title: Biochem Biophys Res Commun. 386 Pages: 153-158
  • Peer Reviewed
• [Journal Article] Regional distribution and the dynamics of n-decanoyl ghrelin, another acyl-form of ghrelin, upon fasting in rodents (2009)
  • Author(s): Hiejima H, Nishi Y, Hosoda H, Yoh J, Mifune H, Satou M, Sugimoto H, Chiba S, Kawahara Y, Tanaka E, Yoshimatsu H, Uchimura N, Kangawa K, Kojima M.
  • Journal Title: Regul Pept. 156 Pages: 47-56
  • Peer Reviewed
• [Presentation] 低エネルギー条件下におけるグレリン遺伝子欠損マウスの体温変動 (2011)
  • Author(s): 佐藤貴弘
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 兵庫県淡路市、淡路夢舞台
  • Year and Date: 2011-09-23
• [Presentation] 低エネルギー条件下におけるグレリン遺伝子欠損マウスの体温変動 (2011)
  • Author(s): 佐藤貴弘、中村祐樹、椎村祐樹、児島将康
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 淡路島(淡路夢舞台)
  • Year and Date: 2011-09-23
• [Presentation] 制限給餌条件下におけるグレリン遺伝子欠損マウスの体温変化 (2011)
  • Author(s): 佐藤貴弘
  • Organizer: 第29回内分泌サマーセミナー
  • Place of Presentation: 仙台市、東北大学医学部
  • Year and Date: 2011-07-08
• [Presentation] 制限給餌条件下におけるグレリン遺伝子欠損マウスの体温変化 (2011)
  • Author(s): 佐藤貴弘、中村祐樹、椎村祐樹、児島将康
  • Organizer: 第29回内分泌サマーセミナー
  • Place of Presentation: 仙台(東北大学医学部)
  • Year and Date: 2011-07-08
• [Presentation] グレリンと体温調節 (2010)
  • Author(s): 児島将康
  • Organizer: 第63回日本薬理学会西南部会「新薬理学セミナー」
  • Place of Presentation: 鹿児島市、鹿児島大学
  • Year and Date: 2010-11-25
• [Presentation] グレリンと体温調節 (2010)
  • Author(s): 児島将康
  • Organizer: 第63回日本薬理学会西南部会「新薬理学セミナー」
  • Place of Presentation: 鹿児島県、鹿児島市、鹿児島大学
  • Year and Date: 2010-11-25
• [Presentation] グレリンと体温調節・肥満 (2010)
  • Author(s): 児島将康
  • Organizer: 第31回日本肥満学会シンポジウム
  • Place of Presentation: 前橋市、前橋テルサ
  • Year and Date: 2010-10-01
• [Presentation] グレリンと体温調節・肥満 (2010)
  • Author(s): 児島将康
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 群馬県、前橋市、前橋テルサ
  • Year and Date: 2010-10-01
• [Presentation] Ten years after the discovery of ghrelin : novel functions and processing (2010)
  • Author(s): 児島将康
  • Organizer: 18th International Symposium of Regulatory Peptidesシンポジウム
  • Place of Presentation: ベルファスト、アイルランド
  • Year and Date: 2010-09-08
• [Presentation] Ten years after the discovery of ghrelin : novel functions and processing (2010)
  • Author(s): Masayasu Kojima
  • Organizer: 18th International Symposium of Regulatory Peptides
  • Place of Presentation: elfast, Ireland, Europa Hotel Conference Center
  • Year and Date: 2010-09-08
• [Presentation] 成長ホルモン分泌と食欲を刺激するホルモン"グレリン"の多彩な生理作用 (2010)
  • Author(s): 児島将康
  • Organizer: 第52回日本小児神経科学会総会
  • Place of Presentation: 福岡市、福岡国際会議場
  • Year and Date: 2010-05-20
• [Presentation] 成長ホルモン分泌と食欲を刺激するホルモン"グレリン"の多彩な生理作用 (2010)
  • Author(s): 児島将康
  • Organizer: 第52回日本小児神経科学会総会
  • Place of Presentation: 福岡県、福岡市、福岡国際会議場
  • Year and Date: 2010-05-20
• [Presentation] Phenotypic analysis of ghrelin knockout mouse (2010)
  • Author(s): 児島将康
  • Organizer: 14th International Congress of Endocrinology(ICE2010)シンポジウム
  • Place of Presentation: 京都府京都市、京都国際会議場
  • Year and Date: 2010-03-29
• [Presentation] Phenotypic analysis of ghrelin knockout mouse (2010)
  • Author(s): 児島将康
  • Organizer: 14th International Congress of Endocrinology(ICE2010)
  • Place of Presentation: 京都府京都市、京都国際会議場
  • Year and Date: 2010-03-29
• [Presentation] Phenotypic analysis of ghrelin knockout mouse (2009)
  • Author(s): 児島将康
  • Organizer: 第82回日本生化学会大会シンポジウム
  • Place of Presentation: 兵庫県神戸市、神戸国際会議場
  • Year and Date: 2009-10-21
• [Presentation] Phenotypic analysis of ghrelin knockout mouse (2009)
  • Author(s): 児島将康
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 兵庫県神戸市、神戸国際会議場
  • Year and Date: 2009-10-21
• [Presentation] Peptide hunting : from Drosophila to Human (2009)
  • Author(s): 児島将康
  • Organizer: Satellite Symposium of 9th VIP/PACAP Symposium in Yakushimaシンポジウム
  • Place of Presentation: 鹿児島県、屋久島いわさきホテル
  • Year and Date: 2009-10-02
• [Presentation] Peptide hunting : from Drosophila to Human (2009)
  • Author(s): 児島将康
  • Organizer: Satellite Symposium of 9th VIP/PACAP Symposium in Yakushima
  • Place of Presentation: 鹿児島県、屋久島いわさきホテル
  • Year and Date: 2009-10-02
• [Patent(Industrial Property Rights)] ショウジョウバエ由来生理活性ペプチド (2010)
  • Inventor(s): 井田隆徳、児島将康、粂和彦
  • Industrial Property Rights Holder: 久留米大学、熊本大学
  • Industrial Property Number: 2010-045816
  • Filing Date: 2010-03-02