Novel treatment for non-alcoholic hepatitis inducing human brown adipose tissue

• Project/Area Number: 26461925
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Jichi Medical University
• Principal Investigator: SAKUMA YASUNARU 自治医科大学, 医学部, 准教授 (10296105)
• Co-Investigator(Kenkyū-buntansha): 三木 厚 自治医科大学, 医学部, 講師 (20570378) ; 安田 是和 自治医科大学, 医学部, 客員教授 (40158001) ; 上本 伸二 京都大学, 医学研究科, 教授 (40252449) ; 笠原 尚哉 自治医科大学, 医学部, 助教 (50382891) ; 寺谷 工 自治医科大学, 医学部, 講師 (70373404) ; 藤本 康弘 京都大学, 医学研究科, 客員研究員 (80335281)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 褐色脂肪細胞 / 表面マーカー / 細胞移植 / 褐色細胞腫 / 肥満治療 / 非アルコール性脂肪肝炎 / 褐色脂肪 / 脂肪肝 / 肥満 / NASH

Outline of Final Research Achievements

Brown adipocytes play a central role in regulating metabolism and generating　metabolic signals. They are also important to maintain metabolic homeostasis by adjusting energy expenditure. However, these cells are not yet well-understood and the tissue-specific presence of uncoupling protein 1 (UCP-1) is a promising lead to gain further understanding. Pheocromocytomas are known to have a tendency to grow into surrounding adipose tissue and become brown adipose tissue. We have successfully collected and cultured these cells from a patient with a pheocromocytoma. There is very little knowledge about Brown adipocytes except for the presence of UCP-1. We performed fluorescence-activated cell sorting combined with a UCP-1 specific aptamer. Cell surface makers were detected using gene-tip analysis and showed CD9, CD177, CD200：positive、and CD40, CD44, CD109: negative.

Research Products

• [Journal Article] Pediatric living donor liver transplantation for congenital hepatic fibrosis using a mother's graft with von Meyenburg complex: A case report. (2016)
  • Author(s): Yamada N, Sanada Y, Katano T, Tashiro M, Hirata Y, Okada N, Ihara Y, Miki A, Sasanuma H, Urahashi T, Sakuma Y, Mizuta K.
  • Journal Title: World J Gastroenterol Volume: 22 Pages: 9865-9870
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemical evaluation for outflow reconstruction using opened round ligament in living donor right posterior sector graft liver transplantation: A case report. (2016)
  • Author(s): Sanada Y
  • Journal Title: World J Gastroenterol Volume: 22(34) Pages: 7851-6
  • DOI: 10.3748/wjg.v22.i34.7851
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Complementary Indicators for Diagnosis of Hepatic Vein Stenosis After Pediatric Living-donor Liver Transplantation. (2016)
  • Author(s): Kawano Youichi
  • Journal Title: Transplant Proc Volume: S0041 Pages: 1156-1161
  • DOI: 10.1016/j.transproceed.2015.12.114
  • Peer Reviewed / Open Access
• [Journal Article] Living-Donor Liver Transplantation Using Segment 2 Monosegment Graft: A Single-Center Experience. (2016)
  • Author(s): Sakuma Y
  • Journal Title: Transplant Proc Volume: 48(4) Pages: 1110-1114
  • DOI: 10.1016/j.transproceed.2015.12.119
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The outcomes of pediatric living donor liver transplantation using small-for-size grafts: experience of a single institute. (2016)
  • Author(s): Yamada N, Sanada Y, Hirata Y, Okada N, Ihara Y, Sasanuma H, Urahashi T, Sakuma Y, Yasuda Y, Mizuta K
  • Journal Title: Pediatr Surg Int Volume: 19 Pages: 363-368
  • DOI: 10.1007/s00383-016-3859-4
  • Peer Reviewed / Open Access
• [Journal Article] Clinical characteristics and outcomes of adenovirus infection of the urinary tract after renal transplantation. (2016)
  • Author(s): Nanmoku K, Ishikawa N, Kurosawa A, Shimizu T, Kimura T, Miki A, Sakuma Y, Yagisawa T
  • Journal Title: Transpl Infect Dis Volume: 18 Pages: 234-239
  • DOI: 10.1111/tid.12519
  • Peer Reviewed / Open Access
• [Journal Article] Selection of Living Donor Liver Grafts for Patients Weighing 6kg or Less (2015)
  • Author(s): Naoya Yamada
  • Journal Title: LIVER TRANSPLANTATION Volume: 21(2) Pages: 233-238
  • DOI: 10.1002/lt.24048
  • Peer Reviewed / Open Access
• [Journal Article] The impact of rituximab in ABOincompatible pediatric living donor liver transplantation: The experience of a single center (2015)
  • Author(s): Noriki Okada, Yukihiro Sanada, Yuta Hirata, Naoya Yamada, Taiichi Wakiya, Yoshiyuki Ihara, Taizen Urahashi, Atsushi Miki, Yuji Kaneda, Hideki Sasanuma, Takehito Fujiwara, Yasunaru Sakuma, Atsushi Shimizu, Masanobu Hyodo, Yoshikazu Yasuda, Koichi Mizuta
  • Journal Title: Pediatric Transplantation Volume: 19 Pages: 279-286
  • DOI: 10.1111/petr.12445
  • Peer Reviewed / Open Access
• [Journal Article] Improved Human Islet Preparations Using Glucocorticoid and Exendin-4 (2014)
  • Author(s): Atsushi Miki
  • Journal Title: Pancreas Volume: 43(8) Pages: 1317-1322
  • DOI: 10.1097/mpa.0000000000000184
  • Peer Reviewed / Open Access
• [Journal Article] Risk Factors of Cytomegalovirus Infection After Pediatric Liver Transplantation (2014)
  • Author(s): Y. Kawano, K. Mizuta, Y. Sanada, T. Urahashi, Y. Ihara, N. Okada, N. Yamada, H. Sasanuma, Y. Sakuma, N. Taniai, H. Yoshida, H. Kawarasaki, Y. Yasuda, and E. Uchida
  • Journal Title: Transplantation Proceedings Volume: 46 Pages: 3543-3547
  • DOI: 10.1016/j.transproceed.2014.09.150
  • Peer Reviewed / Open Access