Integrative omics-based understanding of the appetite-regulating signals within the hypothalamus

• Project/Area Number: 26670458
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Kyoto University
• Principal Investigator: KAZUWA Nakao 京都大学, 医学(系)研究科(研究院), 教授 (00172263)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Tomohiro 京都大学, 大学院医学研究科, 特定准教授 (20402894)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: オミックス / レプチン / 食欲 / 肥満 / シグナル伝達

Outline of Final Research Achievements

We have undertaken phospho-proteomics and metabolomics analyses of the mouse hypothalamus to understand the cross-talk of nutrient signals and phospho-protein signaling. We have established an effective immunoprecipitation method using phospho-tyrosine antibody for the subsequent SDS-PAGE, Ag staining and MS-based annotation. We have already identified multiple novel positive bands in Ag-stained gels that appear by leptin stimulation, which could correspond to novel phosphor-proteins in leptin signaling pathway. In CE/MS-based analysis of the intermediate metabolites in central metabolic pathways revealed a drastic change in nucleic acid and purine metabolism and in pentose-phosphate pathway in hypothalamic samples from mice treated with leptin. Linkage between changes in phosphate group donors and global changes in phospho-proteomics may suggest a novel signaling dynamism of leptin actions in the hypothalamic energy center.

Research Products

• [Journal Article] Increased bone turnover and possible accelerated fracture healing in a murine model with an increased circulating C-type natriuretic peptide. (2015)
  • Author(s): Kondo E, Yasoda A, Fujii T, Nakao K, Yamashita Y, Ueda-Sakane Y, Kanamoto N, Miura M, Arai H, Mukoyama M, Inagaki N, Nakao K
  • Journal Title: Endocrinology Volume: Apr 10 Pages: 00-00
• [Journal Article] Leptin improves fatty liver independently of insulin sensitization and appetite suppression in hepatocyte-specific Pten-deficient mice with insulin hypersensitivity. (2015)
  • Author(s): Yamamoto-Kataoka S, Ebihara K, Aizawa-Abe M, Nishio M, Kusakabe T, Yamamoto Y, Aotani D, Sakai T, Zhao M, Ebihara C, Gumbilai VM, Hosoda K, Suzuki A, Nakao K
  • Journal Title: Horm Metab Res Volume: 47 Issue: 03 Pages: 168-175
  • DOI: 10.1055/s-0034-1395531
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The regulation of circulating ghrelin — with recent updates from cell-based assays [Review] (2015)
  • Author(s): Iwakura H, Kangawa K, Nakao K.
  • Journal Title: Endocrine Journal Volume: 62 Issue: 2 Pages: 107-122
  • DOI: 10.1507/endocrj.EJ14-0419
  • NAID: 130004694065
  • ISSN: 0918-8959, 1348-4540
• [Journal Article] An AKI biomarker lipocalin 2 in the blood derives from the kidney in renal injury but from neutrophils in normal and infected conditions. (2015)
  • Author(s): Kanda J, Mori K, Kawabata H, Kuwabara T, Mori KP, Imamaki H, Kasahara M, Yokoi H, Mizumoto C, Thoennissen NH, Koeffler HP, Barasch J, Takaori-Kondo A, Mukoyama M, Nakao K.
  • Journal Title: Clin Exp Nephrol. Volume: 19 Issue: 1 Pages: 99-106
  • DOI: 10.1007/s10157-014-0952-7
  • NAID: 120005678175
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The G-Protein-Coupled Long-Chain Fatty Acid Receptor GPR40 and Glucose Metabolism (2014)
  • Author(s): T. Tomita, K. Hosoda, J. Fujikura, N. Inagaki, K. Nakao
  • Journal Title: Front Endocrinol (Lausanne). Volume: 5:152 Pages: 1-3
  • DOI: 10.3389/fendo.2014.00152
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of endogenous ACTH on circadian aldosterone rhythm in patients with primary aldosteronism (2014)
  • Author(s): Sonoyama, T., Sone, M. , Tamura, N., Honda, K., Taura, D., Kojima, K., Fukuda, Y., Kanamoto, N., Miura, M., Yasoda, A., Arai, H., Itoh, H., Nakao, K
  • Journal Title: Endocrine Connections Volume: 3 Issue: 4 Pages: 173-179
  • DOI: 10.1530/ec-14-0086
  • Peer Reviewed / Open Access
• [Journal Article] Leptin restores the insulinotropic effect of exenatide in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet (2014)
  • Author(s): T. Sakai, T. Kusakabe, K. Ebihara, D. Aotani, S. Yamamoto-Kataoka, Z. Mingming, VM. Gumbilai, C. Ebihara, M. Aizawa-Abe, Y. Yamamoto, M. Noguchi, J. Fujikura, K. Hosoda, N. Inagaki, K. Nakao
  • Journal Title: Am J Physiol Endocrinol Metab. Volume: 307 Issue: 8 Pages: 712-719
  • DOI: 10.1152/ajpendo.00272.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure. (2014)
  • Author(s): Yamada Y, Kinoshita H, Kuwahara K, Nakagawa Y, Kuwabara Y, Minami T, Yamada C, Shibata J, Nakao K, Cho K, Arai Y, Yasuno S, Nishikimi T, Ueshima K, Kamakura S, Nishida M, Kiyonaka S, Mori Y, Kimura T, Kangawa K, Nakao K.
  • Journal Title: Cardiovasc Research Volume: 104 Issue: 1 Pages: 183-193
  • DOI: 10.1093/cvr/cvu185
  • NAID: 120005619790
  • Peer Reviewed / Open Access
• [Journal Article] The effects of super-flux (high performance) dialyzer on plasma glycosylated pro-B-type natriuretic peptide (proBNP) and glycosylated N-Terminal proBNP in end-stage renal disease patients on dialysis. (2014)
  • Author(s): Nakagawa Y, Nishikimi T, Kuwahara K, Yasuno S, Kinoshita H, Kuwabara Y, Nakao K, Minami T, Yamada C, Ueshima K, Ikeda Y, Okamoto H, Horii K, Nagata K, Kangawa K, Minamino N, Nakao K.
  • Journal Title: PLoS One Volume: 25 Issue: 3 Pages: e92314-e92314
  • DOI: 10.1371/journal.pone.0092314
  • NAID: 120007100132
  • Peer Reviewed / Open Access
• [Journal Article] Macrophage-mediated glucolipotoxicity via myeloid-related protein 8/toll-like receptor 4 signaling in diabetic nephropathy (2014)
  • Author(s): Kuwabara, T., Mori, K., Mukoyama, M., Kasahara, M., Yokoi, H., Nakao, K.
  • Journal Title: Clinical and Experimental Nephrology Volume: impress Issue: 4 Pages: 584-592
  • DOI: 10.1007/s10157-013-0922-5
  • NAID: 120005474441
  • Peer Reviewed
• [Presentation] 食事誘導性肥満の発症におけるリノール酸の効果(ﾎﾟｽﾀｰ) (2014)
  • Author(s): 井上雅文、田中智洋、園山拓洋、中尾一和
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25
• [Presentation] 高脂肪食負荷における食欲制御機構破綻のメカニズム解明の試み(ﾎﾟｽﾀｰ) (2014)
  • Author(s): 園山拓洋、田中智洋、沢田 啓、井上雅文、荻野陽平、Guo Tingting、中尾一和
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: 宮崎
  • Year and Date: 2014-10-24
• [Presentation] Transcriptome Analysis of Arcuate Nucleus from Mice Fed a High-Fat Diet(ﾎﾟｽﾀｰ) (2014)
  • Author(s): T Sonoyama, T Tanaka, H Sawada, M Inoue, Y Ogino, T Guo, K Nakao
  • Organizer: 第3回生命医薬情報学連合大会(IIBMP2014)
  • Place of Presentation: 仙台
  • Year and Date: 2014-10-02
• [Presentation] Transcriptome analysis of arcuate nucleus from mice fed a high-fat diet(ﾎﾟｽﾀｰ) (2014)
  • Author(s): T Sonoyama, T Tanaka, M Inoue, Y Ogino, T Guo, K Nakao
  • Organizer: The Conference on Bioactive Peptides for Cell-Cell Communication 2014
  • Place of Presentation: Kyoto
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] Contribution of dietary linoleic acid intake to the pathogenesis of obesity;in vivo evidence in mice and potential,mechanisms(ﾎﾟｽﾀｰ) (2014)
  • Author(s): M Inoue, T Tanaka, T Sonoyama, K Nakao
  • Organizer: The Conference on Bioactive Peptides for Cell-Cell Communication 2014
  • Place of Presentation: Kyoto
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] 高脂肪食負荷による食欲制御機構破綻のメカニズム解明の試み～トランスクリプトーム解析を中心として～ (2014)
  • Author(s): 園山拓洋、田中智洋、沢田啓、井上雅文、河野裕翔、中尾一和
  • Organizer: 第32回 内分泌代謝学サマーセミナー
  • Place of Presentation: 山梨
  • Year and Date: 2014-07-11
• [Presentation] 食餌誘導性肥満の発症におけるリノール酸の効果(ﾎﾟｽﾀｰ) (2014)
  • Author(s): 井上雅文、田中智洋、園山拓洋、中尾一和
  • Organizer: 第32回内分泌代謝学サマーセミナー
  • Place of Presentation: 山梨
  • Year and Date: 2014-07-11
• [Presentation] 高脂肪食負荷マウスの視床下部弓状核のトランスクリプトーム解析 (2014)
  • Author(s): 園山拓洋、田中智洋、沢田啓、井上雅文、河野裕翔、中尾一和
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪」
  • Year and Date: 2014-05-24
• [Presentation] 高脂肪食負荷マウス視床下部弓状核のトランスクリプトーム解析 (2014)
  • Author(s): 園山拓洋、田中智洋、沢田啓、井上雅文、城孝尚、河野裕翔、中尾一和
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-04-26
• [Presentation] 摂食中枢におけるFGF15と受容体構成分子FGFR4・βKlothoの発現解析(ﾎﾟｽﾀｰ) (2014)
  • Author(s): 田中智洋、河野裕翔、園山拓洋、井上雅文、城孝尚、鍋島陽一、中尾一和
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-04-24