Regulation of obesity and NASH/HCC via glutamine metabolism and its clinical approach(Fostering Joint International Research)

• Project/Area Number: 16KK0197
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Chiba University
• Principal Investigator: Suzuki Sawako 千葉大学, 医学部附属病院, 助教 (60400892)
• Research Collaborator: Prives Carol Clumbia University, Biological Science研究室, 教授 ; Venkatesh Divya Clumbia University, Biological Science研究室, Postdoctoral Research Scientist
• Project Period (FY): 2016 – 2017
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
• Keywords: グルタミン代謝 / 生活習慣病 / 肝癌 / 統合解析 / 細胞死 / 癌 / 糖尿病 / 遺伝子 / 組織 / ゲノム

Outline of Final Research Achievements

We have revealed that GLS2 mediated glutamine metabolism and related to lifestyle diseases and hepatocellular tumorigenesis. In this study, we identified key molecules of GLS2 associated with gluconeogenesis, lipid metabolism, insulin secretion and insulin resistance using the combination of metabolome analysis and RNA sequence analysis. Furthermore, we found GLS2, but not GLS1, showed tumor suppressor function through new cell death different from apoptosis and necrosis by reviewing our research from a global point of view. These results might important to explain the paradox action against tumorigenesis of GLS1 and GLS2.

Research Products

• [Int'l Joint Research] Columbia university(米国) (2017)
  • Year and Date: 2017-02-23
• [Journal Article] Glucagonoma with necrolytic migratory erythema: Metabolic profile and detection of biallelic inactivation of DAXX Gene (2018)
  • Author(s): ①Tamura A, Ogasawara T, Fujii Y, Kaneko H, Nakayama A, Higuchi S, Hashimoto N, Miyabayashi Y, Fujimoto M, Komai E, Kono T, Sakuma I, Nagano H, Suzuki S, Koide H, Yokote K, Iseki K, Oguma R, Matsue H, Nojima H, Sugiura K, Yoshitomi H, Ohtsuka M, Rahmutulla B, Kaneda A, Inoshita N, Ogawa S, Tanaka T.
  • Journal Title: J Clin Endocrinol Metab. Volume: 103 Issue: 7 Pages: 2417
  • DOI: 10.1210/jc.2017-02646
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fracture risk assessment tool (FRAX) and for the diagnosis of osteoporosis in Japanese middle-aged and elderly women: Chiba bone survey (2018)
  • Author(s): Oka R, Ohira M, Suzuki S, Yoshida T, Koide H, Tanaka T, Tatsuno I.
  • Journal Title: Endocrine Journal Volume: 65 Issue: 2 Pages: 193-202
  • DOI: 10.1507/endocrj.EJ17-0331
  • NAID: 130006402991
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Prednisolone-responsive Postpartum IgG4-related Hypophysitis (2018)
  • Author(s): Koide H, Shiga A, Komai E, Yamato A, Fujimoto M, Tamura A, Kono T, Nakayama A, Takiguchi T, Higuchi S, Sakuma I, Nagano H, Hashimoto N, Suzuki S, Takeda Y, Shibuya M, Nishioka H, Yamada S, Inoshita N, Ishiwatari N, Horiguchi K, Yokote K, Tanaka T.
  • Journal Title: Internal Medicine Volume: 57 Issue: 3 Pages: 367-375
  • DOI: 10.2169/internalmedicine.8446-16
  • NAID: 130006329476
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] Multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells causing acromegaly associated with subclinical Cushing's disease: a case report. (2017)
  • Author(s): Takiguchi T, Koide H, Nagano H, Nakayama A, Fujimoto M, Tamura A, Komai E, Shiga A, Kono T, Higuchi S, Sakuma I, Hashimoto N, Suzuki S, Miyabayashi Y, Ishiwatari N, Horiguchi K, Nakatani Y, Yokote K, Tanaka T.
  • Journal Title: BMC Endocr Disord. Volume: 17 Issue: 1 Pages: 54-54
  • DOI: 10.1186/s12902-017-0203-5
  • Peer Reviewed / Open Access
• [Journal Article] SEVEN FAMILIAL DYSALBUMINEMIC HYPERTHYROXINEMIA CASES IN THREE UNRELATED JAPANESE FAMILIES AND HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY ANALYSIS OF THE THYROXINE BINDING PROFILE. (2017)
  • Author(s): Nagano H, Nakagawa Y, Ishikawa N, Watanabe H, Miyabayashi Y, Nakayama A, Fujimoto M, Komai E, Shiga A, Tamura A, Kono T, Takiguchi T, Higuchi S, Sakuma I, Hashimoto N, Suzuki S, Koide H, Yokote K, Tanaka T.
  • Journal Title: Endocr Pract. Volume: 23 Issue: 11 Pages: 1325-1332
  • DOI: 10.4158/ep171964.or
  • Peer Reviewed / Open Access
• [Journal Article] Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells. (2017)
  • Author(s): Ishihara N, Suzuki S, Tanaka S, Watanabe Y, Nagayama D, Saiki A, Tanaka T, Tatsuno I.
  • Journal Title: Mol Med Rep. Volume: 16 Issue: 4 Pages: 4756-4762
  • DOI: 10.3892/mmr.2017.7141
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-140 mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6. (2017)
  • Author(s): Yoshida A, Kitajima S, Li F, Chaoyang C, Yujiro T, Susumu K, Wan Y, Naoyuki H, Hayato M, Nishimoto Y, Nagatani N, Nishiuchi T, Thai T C, Suzuki S, Nakao S, Tanaka T, Hirose O, Barbie D A and Takahashi C.
  • Journal Title: Oncotarget Volume: 印刷中 Issue: 8 Pages: 13872-85
  • DOI: 10.18632/oncotarget.14681
  • NAID: 120006226780
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The RB-IL-6 axis controls self-renewal and endocrine therapy resistance by fine-tuning mitochondrial activity. (2017)
  • Author(s): Kitajima S, Yoshida A, Kohno S, Li F, Suzuki S, Nagatani N, Nishimoto Y, Nishimoto Y, Sasaki N, Muranaka H, Wan Y, Nishiuchi T, Suzuki Y, Tominaga K, Gotoh N, Suzuki M, Ewen M, Baebie D, Hirose O, Tanaka T.
  • Journal Title: Oncogene Volume: impress
  • Peer Reviewed
• [Presentation] The roles of GLS2 in life related disease and liver cancer (2017)
  • Author(s): Sawako Suzuki
  • Organizer: p53 conference
  • Int'l Joint Research
• [Book] がん細胞における特異的細胞内代謝と治療抵抗性 (2017)
  • Author(s): 中山哲俊、鈴木佐和子、田中知明
  • Total Pages: 5
  • Publisher: ニューサイエンス社
• [Book] 内分泌性高血圧疾患診療マニュアル改訂第二版 (2017)
  • Author(s): 鈴木佐和子、横手幸太郎
  • Total Pages: 2
  • Publisher: 診断と治療社
• [Book] 内分泌性高血圧疾患診療マニュアル 改訂第二版 (2017)
  • Author(s): 鈴木佐和子、横手幸太郎
  • Publisher: 診断と治療社
• [Book] 細胞 (2017)
  • Author(s): 中山哲俊、鈴木佐和子、田中知明
  • Publisher: (株)ニューサイエンス社