Inhibitory effect of TACE on WAT browning
Project/Area Number |
16K09759
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | Kumamoto University |
Principal Investigator |
Motoshima Hiroyuki 熊本大学, 大学院生命科学研究部(医), 特任准教授(寄附講座) (40398201)
|
Co-Investigator(Kenkyū-buntansha) |
近藤 龍也 熊本大学, 医学部附属病院, 講師 (70398204)
松村 剛 熊本大学, 大学院生命科学研究部(医), 准教授 (20398192)
井形 元維 熊本大学, 医学部附属病院, 寄附講座教員 (40599099)
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Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | ブラウニング / TNFα変換酵素 / 白色脂肪組織 / 肥満 / 糖尿病 / 炎症 / インスリン抵抗性 / リモデリング / シグナル伝達 / 脂肪細胞 |
Outline of Final Research Achievements |
Acetate induces browning in WAT of obese mice but its effect is small. It has not been investigated whether TNFα-converting enzyme (TACE) could affect to the browning of visceral white adipose tissue (WAT) in obese mice given a high-fat diet (HFD) and enhance the acetate-induced browning of WAT. Feeding of a HFD induced obesity in C57BL6 mice and increased the expression of TNFα, TACE and inducible NO synthase (iNOS) in WAT. Acetate and TACE inhibitors could induce browning in the mice fed with HFD. We observed the additional effect of acetate and the inhibitor on browning. TNFα, TACE and iNOS expressed at the higher level in stromal vascular fraction that in adipocyte fraction, especially in macrophages. An iNOS inhibitor, 1400W, could suppress the expression and activity of TACE in WAT of mice fed HFD and in macrophages derived from bone marrow. These results may indicate that inflammatory signal via TNF receptor-iNOS in WAT of obese mice triggers the induction of TACE in WAT.
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Academic Significance and Societal Importance of the Research Achievements |
内臓脂肪組織におけるTACEの発現や活性がTNFα→TNFα受容体→JNK活性化→iNOS誘導により促進されること、肥満で活性化した同経路を阻害することでWATブラウニングが促進できるかも知れないという実験結果は、国内外を通じ未報告であり、当該分野におけるインパクトは大きい。酢酸によるブラウニング刺激効果がiNOS阻害やTACEの阻害によって導けることも報告されていない。様々な抗炎症作用を示す薬剤がiNOS抑制を介したTACE活性抑制を実現できる可能性があり、本研究が提唱したストラテジーは大きな広がりが期待できる。臨床応用を勘案した基礎データの蓄積が必要である。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Impact of hepatic HSP72 on insulin signaling2019
Author(s)
Kitano Sayaka、Kondo Tatsuya、Matsuyama Rina、Ono Kaoru、Goto Rieko、Takaki Yuki、Hanatani Satoko、Sakaguchi Masaji、Igata Motoyuki、Kawashima Junji、Motoshima Hiroyuki、Matsumura Takeshi、Kai Hirofumi、Araki Eiichi
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Journal Title
American Journal of Physiology-Endocrinology and Metabolism
Volume: 316
Issue: 2
Pages: E305-E318
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of microRNA that represses IRS-1 expression in liver.2018
Author(s)
Ono K, Igata M, Kondo T, Kitano S, Takaki Y, Hanatani S, Sakaguchi M, Goto R, Senokuchi T, Kawashima J, Furukawa N, Motoshima H, Araki E
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Journal Title
PLoS One
Volume: 13
Issue: 1
Pages: 0191553-0191553
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of local macrophage growth ameliorates focal inflammation and suppresses atherosclerosis.2018
Author(s)
Yamada S, Senokuchi T, Matsumura T, Morita Y, Ishii N, Fukuda K, Murakami S, Nishida S, Kawasaki S, Motoshima H, Furukawa N, Komohara Y, Fujiwara Y, Koga T, Yamagata K, Takeya M, Araki E
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Journal Title
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume: 印刷中
Issue: 5
Pages: 994-1006
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Acetate alters expression of genes involved in beige adipogenesis in 3T3-L1 cells and obese KK-Ay mice2016
Author(s)
Hanatani S, Motoshima H, Takaki Y, Kawasaki S, Igata M, Matsumura T, Kondo T, Senokuchi T, Ishii N, Kawashima J, Kukidome D, Shimoda S, Nishikawa T, Araki E
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Journal Title
J Clin Biochem Nutr
Volume: 59
Pages: 207-214
NAID
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Activation of heat shock response to treat obese subjects with type 2 diabetes: a prospective, frequency-escalating, randomized, open-label, triple-arm trial.2016
Author(s)
Kondo T, Goto R, Ono K, Kitano S, Suico MA, Sato M, Igata M, Kawashima J, Motoshima H, Matsumura T, Kai H, Araki E.
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Journal Title
Sci Rep.
Volume: 19
Issue: 1
Pages: 35690-35690
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Coexistence of resistance to thyroid hormone and papillary thyroid carcinoma2016
Author(s)
Igata M, Tsuruzoe K, Kawashima J, Kukidome D, Kondo T, Motoshima H, Shimoda S, Furukawa N, Nishikawa T, Miyamura N, Araki E
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Journal Title
Endocrinology, Diabetes & Metabolism
Volume: 2016
Pages: 160003-160003
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Impacts of the Kumamoto Earthquake 2016 on glycemic control in diabetic patients.2018
Author(s)
Kondo T, Miyakawa N, Motoshima H, Ishii N, Igata M, Yoshinaga K, Kukidome D, Senokuchi T, Kawashima J, Matsumura T, Araki E
Organizer
The 78th ADA Scientific Meetng
Related Report
Int'l Joint Research
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[Presentation] Obesity-induced microRNA-222 impairs insulin signaling through the repression of IRS-1 expression in hepatocytes.2017
Author(s)
Ono K, Igata M, Kondo T, Kitano S, Takaki Yuki, Hanatani S, Goto R, enokuchi T, Kawashima J, Furukawa N, Motoshima H, ArakiE
Organizer
The 53th EASD Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] The therapeutic potential of heat shock protein 72 in mice model of type 2 diabetes.2017
Author(s)
Kondo T, Kitano S, MIyakawa N, Goto R, Ono K, Igata M, Kawashima J, Motoshima H, Matsumura T, Kai H, ArakiE
Organizer
IDF congress 2017
Related Report
Int'l Joint Research
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[Presentation] 熊本地震の糖尿病関連入院への影響 ―入院レセプトデータからの入院理由・数の推定と被災患者支援のあり方―.2017
Author(s)
本島寛之, 石井規夫, 西田健朗, 河島淳司, 久保田恭鼓, 久木留大介, 井形元維, 佐田公範, 花谷聡子, 高木優樹, 可徳美里, 三島裕子, 瀬ノ口隆文, 近藤龍也, 松村剛, 荒木栄一
Organizer
第60回日本糖尿病学会年次学術集会
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[Presentation] 酢酸の経口摂取による抗肥満作用の検討2016
Author(s)
花谷聡子, 本島寛之, 井形元維, 川崎修二, 高木優樹, 河島淳司, 近藤龍也, 吉永佳代, 瀬ノ口隆文, 荒木栄一
Organizer
第54回日本糖尿病学会九州地方会
Place of Presentation
かごしま県民交流センター、鹿児島市
Year and Date
2016-10-14
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[Presentation] Aldosterone excess state causes a chronic inflammation in pancreatic islet and eplerenone protects islet via GLP-1 secretion2016
Author(s)
Goto R, Kondo T, Kitano S, Ono K, Kawashima J, Matsumura T, Motoshima H, Araki E
Organizer
ISH 2016 satellite symposium, Renin-angiotensin-aldosterone system (RAAS)
Place of Presentation
Congress Square Nihonbashi, Tokyo, Japan
Year and Date
2016-09-23
Related Report
Int'l Joint Research
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[Presentation] Activation of Heat Shock Response Provided by Mild Electrical Stimulation with Heat Shock Improves Metabolic Abnormalities in Obese Subjects with Type 2 Diabetes2016
Author(s)
Kondo T, Goto R, Ono K, Kitano S, Igata M, Kawashima J, Motoshima H, Matsumura T, Kai H, Araki E
Organizer
52th EASD Annual Meeting
Place of Presentation
Messe Munchen, Munich, Germany
Year and Date
2016-09-12
Related Report
Int'l Joint Research
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[Presentation] 熊本の糖尿病・生活習慣病予防の取組,「ブルーサークル メニュー(BCM)開発」の新たな展開~BCM社員食堂版 の効果~2016
Author(s)
本島寛之, 毛井順子, 宮田真理子, 三浦幸輔, 前中あおい, 三島裕子, 久木留大介, 川島隆文, 後藤理英子, 吉村沢子, 長瀬博美, 福田伴美, 白坂亜子, 関上泰二, 下田誠也, 岸川秀樹, 村岡まき子, 下村弘之, 猪原淑子, 柿村葉子, 荒木栄一
Organizer
第59回日本糖尿病学会年次学術集会
Place of Presentation
京都国際会議場、京都市
Year and Date
2016-05-19
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[Presentation] 正常およびGTG誘発性肥満マウスの肝における既知の細胞老化マーカーの検討2016
Author(s)
本島寛之, 高木優樹, 花谷聡子, 川崎修二, 井形元維, 吉永佳代, 河島淳司, 瀬ノ口隆文, 近藤龍也, 松村剛, 古川昇, 荒木栄一
Organizer
第3回肝臓と糖尿病・代謝研究会
Place of Presentation
石川県立音楽堂、野々市
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