Analysis of growth and differentiation network system for immune cells of adipocyte by hormone during childhood

• Project/Area Number: 24591515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Oita University (2014-2016); Kyushu University (2012-2013)
• Principal Investigator: Ihara Kenji 大分大学, 医学部, 教授 (80294932)
• Co-Investigator(Kenkyū-buntansha): 石井 加奈子 九州大学, 大学病院, 学術研究員 (90400332)
• Project Period (FY): 2012-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 成長ホルモン / 脂肪細胞 / 免疫細胞 / メタボローム / マクロファージ / ネットワーク / アディポネクチン / 肥満 / 脂肪

Outline of Final Research Achievements

We studied growth hormone (GH) for the differentiation and proliferation of adipocytes via activation of monocytes. Pretreatment with GH, RAW 264 cells decreased the degree of reduction of adiponectin production when co-cultured with adipocytes. It was presumed that some humoral factors produced by macrophage with GH stimulation had influenced on adiponectin expression from adipocytes. Next, metabolome analysis of the produced factors from RAW 264 cell with or without GH treatment suggested the significant changes in amino acid metabolites (such as glutamine and glutamic acid) in the TCA cycle.

Research Products

• [Journal Article] Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann, Sotos and Kabuki syndromes: A nationwide survey in Japan (2017)
  • Author(s): Toda N, Ihara K, Kojima-Ishii K, Ochiai M, Ohkubo K, Kawamoto Y Kohno Y, Kumasaka S, Kawase A, Ueno Y, Futatani T, Miyazawa T, Nagaoki Y, Nakata S, Misaki M, Arai H, Kawai M, Sato M, Yada Y, Takahashi N., Komatsu A, Maki K, Watabe S, Sumida Y, Kuwashima M, Mizumoto H, Sato K, Hara T
  • Journal Title: Am J Med Genet Volume: 173 Pages: 360-367
  • DOI: 10.1002/ajmg.a.38011
  • Peer Reviewed
• [Journal Article] FUT2 Nonsecretor Status Links Type 1 Diabetes Susceptibility in Japanese children (2017)
  • Author(s): Ihara K, et al.
  • Journal Title: Diabet Med Volume: 34 Pages: 586-589
  • DOI: 10.1111/dme.13288
  • Peer Reviewed
• [Journal Article] A severe pulmonary complication in a patient with COL4A1-related disorder: A case report. (2017)
  • Author(s): Abe Y, Matsuduka A, Okanari K, Miyahara H, Kato M, Miyatake S, Saitsu H, Matsumoto N, Tomoki M, Ihara K
  • Journal Title: Eur J Med Genet. Volume: 60 Pages: 169-17
  • DOI: 10.1016/j.ejmg.2016.12.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Syndromic Adrenal Hypoplasia Caused by Activating SAMD9 Mutations (2016)
  • Author(s): Narumi S*, et al., Matsumoto N, et al.
  • Journal Title: Nature Genetics Volume: 48 Pages: 792-7
  • DOI: 10.1038/ng.3569
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Blood Reference Intervals for Preterm Low-Birth-Weight Infants: A Multicenter Cohort Study in Japan. (2016)
  • Author(s): Ochiai M, Matsushita Y, Inoue H, Kusuda T, Kang D, Ichihara K, Nakashima N, Ihara K, Ohga S, Hara T
  • Journal Title: PLoS One. Volume: 11
  • DOI: 10.1371/journal.pone.0161439
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Activation of an Innate Immune Receptor, Nod1, Accelerates Atherogenesis in Apoe-/- Mice. (2015)
  • Author(s): Kanno S, Nishio H, Tanaka T, Motomura Y, Murata K, Ihara K, Onimaru M, Yamasaki S, Kono H, Sueishi K, Hara T
  • Journal Title: J Immunol Volume: 194 Pages: 773-780
  • Peer Reviewed
• [Journal Article] ＴYK2 Promoter Variant and Diabetes Mellitus in the Japanese. (2015)
  • Author(s): Nagafuchi S, Kamada-Hibio Y, Hirakawa K, Tsutsu N, Minami M, Okada A, Kai K, Teshima M, Moroishi A, Murakami Y, Umeno Y, Yokogawa Y, Kogawa K, Izumi K, Anzai K, Iwakiri R, Hamaguchi K, Sasaki N, Nohara S, Yoshida E, Harada M, Akashi K, Yanase T, Ono J, Okeda T, Fujimoto R, Ihara K, et al.
  • Journal Title: EBioMedicine. Volume: 2 Pages: 744-749
  • DOI: 10.1016/j.ebiom.2015.05.004
  • Peer Reviewed / Open Access
• [Journal Article] Moyamoya disease susceptibility gene RNF213 links inflammatory and angiogenic signals in endothelial cells. (2015)
  • Author(s): Ohkubo K, Sakai Y, Inoue H, Akamine S, Ishizaki Y, Matsushita Y, Sanefuji M, Torisu H, Ihara K, Sardiello M, Hara T
  • Journal Title: Sci Rep Volume: 5 Pages: 13191-13191
  • DOI: 10.1038/srep13191
  • Peer Reviewed
• [Journal Article] The First Nationwide Survey and Genetic Analyses of Bardet-Biedl Syndrome in Japan. (2015)
  • Author(s): Hirano M, Satake W, Ihara K, Tsug I, Kondo S, Saida K, Betsui H, Okubo K, Sakamoto H, Ueno S, Ikuno Y, Ishihara R, Iwahashi H, Ohishi M, Mano T, Yamashita T, Suzuki Y, Nakamura Y, Kusunoki S, Toda T
  • Journal Title: PLoS One Volume: 10
  • DOI: 10.1371/journal.pone.0136317
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Survival and neurodevelopmental outcome of preterm infants born at 22-24 weeks of gestational age (2014)
  • Author(s): Ochiai M, Kinjo T, Takahata Y, Iwayama M, Abe T, Ihara K, Ohga S, Fukushima K, Kato K, Taguchi T, Hara T
  • Journal Title: Neonatology. Volume: 10 Pages: 79-84
  • DOI: 10.1159/000355818
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Endocrine and metabolic abnormalities in a patient with childhood Werner syndrome (2014)
  • Author(s): Toda N, Ihara K, Takemoto M, Yokote K, Hara T.
  • Journal Title: J Am Geriatr Soc. Volume: 62 Pages: 1404-1405
  • DOI: 10.1111/jgs.12897
  • Peer Reviewed
• [Journal Article] Thyroid Follicular Carcinoma in a Fourteen-year-old Girl with Graves’ Disease (2014)
  • Author(s): Kojima-Ishii K, Ihara K, Ohkubo K, Matsuo T, Toda N, Yamashita H, Kono S, Hara T
  • Journal Title: Clin Pediatr Endocrinol Volume: 23 Issue: 2 Pages: 59-64
  • DOI: 10.1297/cpe.23.59
  • NAID: 130004853603
  • ISSN: 0918-5739, 1347-7358
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of p53 but not Rb in the cytoplasm of neurons and small vessels in an autopsy of a patient with Cockayne syndrome. (2014)
  • Author(s): Miyahara H, Itonaga T, Maeda T, Izumi T, Ihara K
  • Journal Title: Neuropathology. Volume: in press
  • DOI: 10.1111/neup.12183
  • Peer Reviewed
• [Journal Article] Hyperinsulinemic hypoglycemia of infancy in Sotos syndrome (2013)
  • Author(s): Matsuo T, Ihara K, Ochiai M, Kinjo T, Yoshikawa Y, Kojima-Ishii K, Noda M, Mizumoto H, Misaki M, Minagawa K, Tominaga K, Hara T
  • Journal Title: Am J Med Genet A Volume: 161A(1) Pages: 34-37
  • DOI: 10.1002/ajmg.a.35657
  • Peer Reviewed
• [Journal Article] Coagulopathy in patients with late-onset ornithine transcarbamylase deficiency in a remission state: a previously unrecognized complication. (2013)
  • Author(s): Ihara K
  • Journal Title: Pediatrics Volume: 131
  • DOI: 10.1542/peds.2012-0030
  • Peer Reviewed
• [Journal Article] Left ventricular efficiency after ligation of patent ductus arteriosus for premature infants. (2013)
  • Author(s): Nagata H, Ihara K, Yamamura K, Tanoue Y, Shiokawa Y, Tominaga R, Hara T
  • Journal Title: J Thorac Cardiovasc Surg Volume: 146(6): Pages: 1353-8
  • DOI: 10.1016/j.jtcvs.2013.02.019
  • Peer Reviewed
• [Journal Article] Fatigue and quality of life in citrin deficiency during adaptation and compensation period. (2013)
  • Author(s): Okano Y, Kobayashi K, Ihara K, Ito T, Yoshino M, Watanabe Y, Kaji S, Ohura T, Nagao M, Noguchi A, Mushiake S, Hohashi N, Hashimoto-Tamaoki T
  • Journal Title: Mol Genet Metab Volume: 109(1) Pages: 9-13
  • DOI: 10.1016/j.ymgme.2013.01.020
  • Peer Reviewed
• [Journal Article] Hypothalamic pituitary complications in Kabuki syndrome. (2013)
  • Author(s): Ito N, Ihara K, Tsutsumi Y, Miyake N, Matsumoto N, Hara T
  • Journal Title: Pituitary Volume: in press
  • Peer Reviewed
• [Journal Article] Two neonatal cholestasis patients with mutations in the SRD5B1(AKR1D1) gene: diagnosis and bile acid profiles during chenodeoxycholic acid treatment. (2013)
  • Author(s): Seki Y, Mizuochi T, Kimura A, Takahashi T, Ohtake A, Hayashi S, Morimura T, Ohno Y, Hoshina T, Ihara K, Takei H, Nittono H, Kurosawa T, Homma K, Hasegawa T, Matsuishi T
  • Journal Title: J Inherit Metab Dis Volume: in press
  • Peer Reviewed
• [Journal Article] Genetic susceptibility to Kawasaki disease: Analysis of pattern recognition receptor genes. (2012)
  • Author(s): Onoyama S, Ihara K, Yamaguchi Y, Ikeda K, Yamaguchi K, Yamamura K, Hoshina T, Mizuno Y, Hara T
  • Journal Title: Hum Immunol Volume: 73 Pages: 654-60
  • DOI: 10.1016/j.humimm.2012.03.011
  • Peer Reviewed
• [Journal Article] Histo-blood group gene polymorphisms as potential genetic modifiers of the development of coronary artery lesions in patients with Kawasaki disease. (2012)
  • Author(s): Yamamura K, Ihara K, Ikeda K, Nagata H, Mizuno Y, Hara T
  • Journal Title: Int J Immunogenet Volume: 39 Pages: 119-25
  • DOI: 10.1016/j.ijcard.2012.03.021
  • Peer Reviewed
• [Journal Article] Endocrine complications in primary immunodeficiency diseases in Japan (2012)
  • Author(s): Hoshina T
  • Journal Title: Clin Endocrinol Volume: 73 Pages: 628-34
  • DOI: 10.1111/j.1365-2265.2012.04390.x
  • Peer Reviewed
• [Journal Article] HLA-Class II and Class I Genotypes among Japanese Children with Type 1A Diabetes and Their Families. (2012)
  • Author(s): Sugihara S
  • Journal Title: Pediatr Diabetes Volume: 13 Pages: 33-4
  • DOI: 10.1111/j.1399-5448.2011.00833.x
  • Peer Reviewed
• [Presentation] 小児科診療のための臨床遺伝学と臨床カウンセリングの基礎知識 (2016)
  • Author(s): 井原健二
  • Organizer: 日本小児科学会佐賀地方会
  • Place of Presentation: 佐賀大学医学部臨床講堂（佐賀県佐賀市）
  • Invited
• [Presentation] 脂質代謝と成長ホルモン：免疫細胞を介した調節メカニズムの探究 (2015)
  • Author(s): 井原健二
  • Organizer: 宮崎代謝内分泌研究会
  • Place of Presentation: 宮崎大学医学部（宮崎県清武町）
  • Year and Date: 2015-03-20
  • Invited
• [Presentation] 日常診療に潜む稀少疾患－小児内分泌・代謝疾患を察知する－ (2014)
  • Author(s): 井原健二
  • Organizer: 第67回九州小児科学会
  • Place of Presentation: 大分県労働福祉会館（大分県大分市）
  • Year and Date: 2014-11-22 – 2014-11-23
  • Invited
• [Presentation] SGA性低身長に対するGH治療による代謝・免疫学的影響の検討 (2014)
  • Author(s): 石井加奈子、井原健二、大久保一宏、松尾光通、戸田尚子、原 寿郎
  • Organizer: 第87回日本内分泌学会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 遅発型 Ornithine Transcarbamylase (OTC) 欠損症に潜在する凝固異常 (2013)
  • Author(s): 井原健二、芳野信、保科隆之、原田なをみ、石井加奈子、長谷川有紀、渡辺順子、山口清次、原寿郎
  • Organizer: 第116回日本小児科学会
  • Place of Presentation: 広島
• [Presentation] 新生児一過性高インスリン性低血糖はSotos症候群の重要な臨床的特徴である (2013)
  • Author(s): 井原 健二、松尾 光通、吉川 陽子、落合 正行、金城 唯宗、石井加奈子、原 寿郎、水本 洋、野田 麻里絵、富永 康仁、三﨑 真生子
  • Organizer: 第86回日本内分泌学会
  • Place of Presentation: 仙台
• [Presentation] 日本人小児１型糖尿病の疾患感受性遺伝子の探求：ABO型とLewis型血液型抗原の関与 (2013)
  • Author(s): 井原健二、深野智華、戸田尚子、原寿郎、綾部匡之、深見真紀、杉原茂孝、緒方勤、雨宮伸
  • Organizer: 第47回日本小児内分泌学会
  • Place of Presentation: 東京
• [Presentation] 新生児一過性高インスリン性低血糖はSotos症候群の重要な臨床的特徴である (2013)
  • Author(s): 井原 健二、松尾 光通、吉川 陽子、落合 正行、金城 唯宗、石井加奈子、原 寿郎、水本 洋、野田 麻里絵、富永 康仁、三﨑 真生子
  • Organizer: 第58回日本人類遺伝学会
  • Place of Presentation: 仙台
• [Presentation] エコチル調査と小児内分泌・代謝疾患 胎児期および幼少期における環境と肥満、インスリン抵抗性、2型糖尿病の発生 (2012)
  • Author(s): 井原健二
  • Organizer: 第115回日本小児科学会
  • Place of Presentation: 福岡
• [Presentation] とっておきの症例：多腺性自己免疫症候群III型の母娘例 (2012)
  • Author(s): 井原健二
  • Organizer: 第46回日本小児内分泌学会
  • Place of Presentation: 大阪
  • Invited
• [Presentation] 脂質代謝におけるSTAT5B遺伝子の役割 (2012)
  • Author(s): 井原健二
  • Organizer: 第26回 日本小児脂質研究会
  • Place of Presentation: 川越
  • Invited
• [Presentation] SGA性低身長に対するGH治療による血液・免疫学的影響の検討 (2012)
  • Author(s): 石井加奈子、井原健二、牧村美佳、野崎高史、大久保一宏、松尾光通、原 寿郎
  • Organizer: 第115回日本小児科学会
  • Place of Presentation: 福岡
• [Presentation] 成長ホルモン分泌不全における脂質代謝に関与する遺伝的背景因子の解析 (2012)
  • Author(s): 井原健二、牧村美佳、石井加奈子、大久保一宏、野崎高史、原寿郎、河野斉
  • Organizer: 第115回日本小児科学会
  • Place of Presentation: 福岡
• [Presentation] こどもの生活習慣病を予防する
  • Author(s): 井原健二
  • Organizer: 第44回日本小児感染症学会総会・学術集会 市民公開講座
  • Place of Presentation: 福岡
  • Invited
• [Presentation] 遺伝に関する基礎知識と遺伝カウンセリングについて
  • Author(s): 井原健二
  • Organizer: 新型出生前診断の導入を考える：西南大学公開シンポジウム
  • Place of Presentation: 福岡
  • Invited
• [Book] 今日の治療指針2016年版 先天性甲状腺機能低下症 (2016)
  • Author(s): 井原健二
  • Publisher: 医学書院
• [Book] 今日の小児治療指針：褐色細胞腫 (2015)
  • Author(s): 井原健二
  • Publisher: 医学書院
• [Book] 乳児期以降の低血糖（分担），ワンランク上の小児内分泌疾患 (2013)
  • Author(s): 井原健二（分担）
  • Publisher: 総合医学社
• [Book] Cushing症候群（分担） 今日の小児治療指針 第15版 (2012)
  • Author(s): 井原健二
  • Publisher: 医学書院
• [Book] 糖原病（分担），最新ガイドライン準拠 小児科 診断・治療指針 (2012)
  • Author(s): 井原健二
  • Publisher: 中山書店