Molecular mechanism of beige adipocyte differentiation and activation
| Project/Area Number |
17K19919
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Health science and related fields
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
花田 礼子 大分大学, 医学部, 教授 (00343707)
波田 一誠 大分大学, 医学部, 助教 (00546202)
西田 欣広 大分大学, 医学部, 准教授 (10336274)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | 脂肪細胞 / 肥満 / 代謝疾患 / マウス疾患モデル / ベージュ脂肪細胞 / ボンベシン様ペプチド / 遺伝子欠損マウス / CD105 / ペプチド / TGF-β / 代謝 / 細胞生物学 |
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| Outline of Final Research Achievements |
We investigated molecules involved in the differentiation and activation of beige adipocyte, a thermogenic adipocyte located in white adipose tissue. From the data of Gene expression profile analysis between white adipocytes and beige adipocytes, we first focused on CD105. We found that CD105 maintains differentiation into beige adipocytes by inhibiting Smad2 activation (Higa et al., Mol. Cell. Endocrinol, 2018). Next, we also focused on Neuromedin B (NMB) and Gastrin Releasing Peptide (GRP), which are bombesin-like peptides. We generated knockout mice lacking the genes for both molecules. We found that the mice lacking the NMB gene had increased Thermo production in brown adipose tissue and suppressed high-fat diet-induced weight gain and ectopic fat accumulation in the liver. These data suggest that these molecules may be the therapeutic target for obesity and its related metabolic diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
ベージュ脂肪細胞は、寒冷刺激などの環境刺激において白色脂肪組織中に出現し、発熱やエネルギー消費に関与する。特に成人においては褐色脂肪細胞よりむしろベージュ脂肪細胞がエネルギー代謝に関与するため、肥満症や代謝異常症の治療標的として注目されている。しかしその分化機構に関しては未だ不明な点が多い。本研究において、CD105からのSmadシグナル伝達機構がベージュ脂肪細胞の分化に重要であること、ボンベシン様ペプチドのNMBとGRPがベージュ脂肪を介して肥満を抑制することが示唆された。これらの分子を標的として、新たな抗肥満薬・代謝改善薬の開発につながることが期待される。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Cocaine has some effect on Neuromedin U expressing neurons related to the brain reward system.2020
Author(s)
Anan M, Higa R, Shikano K, Shide M, Soda A, Apolinario MEC, Mori K, Shin T, Miyazato M, Mimata H, Hikida T, Hanada T, Nakao K, Kangawa K and Hanada R
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Journal Article] CLP1 acts as the main RNA kinase in mice2020
Author(s)
Fujinami H, Shiraishi H, Hada K, Inoue M, Morisaki I, Higa R, Shin T, Kobayashi T, Hanada R, Penninger JM, Mimata H, Hanada T.
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Journal Title
Biochem Biophys Res Commun.
Volume: 525
Issue: 1
Pages: 129-134
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] AIF-regulated oxidative phosphorylation supports lung cancer development2019
Author(s)
Rao S, Mondragon L, Pranjic B, Hanada T, Stoll G, Sica V,Modjtahedi N, Pai TP, Onji M, Uribesalgo I, Hanada R, Koglgruber R, Cronin SJ, Kroemer G, Penninger JM et al.
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Journal Title
Cell Res. 2019 Jul;29(7):579-591. doi: 10.1038/s41422-019-0181-4. Epub 2019 May 27.
Volume: 29
Issue: 7
Pages: 579-591
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CD105 maintains the thermogenic program of beige adipocytes by regulating Smad2 signaling2018
Author(s)
Higa R, Hanada T, Teranishi H, Miki D, Seo K, Hada K, Shiraishi H, Mimata H, Hanada R, Kangawa K, Murai T, Nakao K.
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Journal Title
Molecular and Cellular Endocrinology
Volume: 印刷中
Pages: 184-193
DOI
Related Report
Peer Reviewed / Open Access
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