Effects of thyroid hormone on energy metabolism-related gene transcription

• Project/Area Number: 15K09436
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kochi University
• Principal Investigator: Iwasaki Yasumasa 高知大学, 教育研究部医療学系臨床医学部門, 教授 (30303613)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 甲状腺ホルモン / 糖代謝 / 脂質代謝 / エネルギー代謝 / 遺伝子転写調節 / ミトコンドリア / 解糖系 / 脂質合成系 / 脂質分解系 / ペントースリン酸回路 / 脂肪酸合成 / 中性脂肪合成

Outline of Final Research Achievements

We have tried to elucidate the molecular mechanism of thyroid hormone (T3)-induced energy metabolism by comprehensive analysis of T3-targete genes. Among the carbohydrate, lipid, and mitochondria-related genes, we have identified T3-inducible genes as follows: glycolysis/PPP(GK,PFK2,G6PD), mitochondria（POLG1,NRF2,Tfam,CYC1,UCPs,ANTs),FFA synthesis (CS,ACLY,ACC,FAS,SCD),TG synthesis/catabolism (ME,THRP,GPD1,GPAT3, HSL). Then we have focused on the de novo T3-target gene GPAT3 and further examined the mechanism of T3 effect on GPAT3 gene transcription. We identified a TRE on its promoter (DR4 type,-447/-432bp) and confirmed its role by deletion analysis and gel shift assay. Overall, T3 indues a variety of metabolic genes, and facilitate both anabolic and catabolic facets of energy metabolism.

Research Products

• [Journal Article] CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα. (2016)
  • Author(s): Nakagawa Y, Satoh A, Tezuka H, Han SI, Takei K, Iwasaki H, Yatoh S, Yahagi N, Suzuki H, Iwasaki Y, Sone H, Matsuzaka T, Yamada N, Shimano H.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 39182-39182
  • DOI: 10.1038/srep39182
  • NAID: 120007135285
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Diagnosis and treatment of adrenal insufficiency including adrenal crisis: a Japan Endocrine Society clinical practice guideline [Opinion] (2016)
  • Author(s): Yanase T, Tajima T, Katabami T, Iwasaki Y, Tanahashi Y, Sugawara A, Hasegawa T, Mune T, Oki Y, Nakagawa Y, Miyamura N, Shimizu C, Otsuki M, Nomura M, Akehi Y, Tanabe M, Kasayama S.
  • Journal Title: Endocrine Journal Volume: 63 Issue: 9 Pages: 765-784
  • DOI: 10.1507/endocrj.EJ16-0242
  • NAID: 130005597967
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Molecular Mechanism of thyroid hormone-mediated cellular energy metabolism: Role of mitochondrial adenine nucleotide translocators (2015)
  • Author(s): Iwasaki Y, Nishiyama M.
  • Organizer: 15th International Thyroid Congress
  • Place of Presentation: Orlando, Florida
  • Year and Date: 2015-10-18
  • Int'l Joint Research