Shedding of TNF receptors in adipose tissues and insulin resistance

• Project/Area Number: 25461360
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kumamoto University
• Principal Investigator: MOTOSHIMA HIROYUKI 熊本大学, 医学部附属病院, 助教 (40398201)
• Co-Investigator(Kenkyū-buntansha): MATSUMURA Takeshi 熊本大学, 医学部附属病院, 講師 (20398192) ; NISHIKAWA Takeshi 独立行政法人国立病院機構熊本医療センター(臨床研究部), その他部局等, その他 (70336212) ; KONDO Tatsuya 熊本大学, 生命科学研究部, 講師 (70398204)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肥満 / 脂肪細胞 / TNF-R1 / 炎症 / サイトカイン / メタボリックシンドローム / インスリン抵抗性 / ２型糖尿病 / TNF１型受容体 / ADAM-8 / ２型糖尿病発症

Outline of Final Research Achievements

TNFα is involved in obesity-induced insulin resistance. The biological activities are mediated via two distinct receptors, TNFR1 and TNFR2. TNFR1 mainly initiates either pro-inflammatory or pro-apoptotic signals in many tissues. A previous work demonstrated that a disintegrin and metalloproteinase 8 (ADAM8) works as a TNFR1 sheddase and produced neuro-protections. However, it has not been tested whether ADAM8 cleaves TNFR1 in adipose and liver tissues in obesity. We investigated whether AMAM8 affects TNFR1 shedding to measure TNFR1 in cell experiments. Both of diet-induced obesity and gold-thioglucose-induced hyperphagic mice showed increased expression of ADAM8 mRNA. Either TNFα or LPS treatment increased TNFR1 shedding in 3T3-L1 and HepG2 cells. However, adenoviral overexpression of ADAM8 or addition of purified ADAM8 protein to culture media did not affect TNFα- or LPS-induced TNFR1 shedding, indicated that ADAM8 may not work as a TNFR1 sheddase in adipocytes and liver.

Research Products

• [Journal Article] Insulin requirement profiles in Japanese hospitalized subjects with type 2 diabetes treated with basal-bolus insulin therapy (2015)
  • Author(s): Shimoda S, Okubo M, Koga K, Sekigami T, Kawashima J, Kukidome D, Igata M, Ishii N, Shimakawa A, Matsumura T, Motoshima H, Furukawa N, Nishida K, Araki E
  • Journal Title: Endocrine Journal Volume: 62 Issue: 2 Pages: 209-216
  • DOI: 10.1507/endocrj.EJ14-0487
  • NAID: 130004704365
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation. (2014)
  • Author(s): Fukuda K, Matsumura T, Senokuchi T, Ishii N, Kinoshita H, Yamada S, Murakami S, Nakao S, Motoshima H, Kondo T, Kukidome D, Kawasaki S, Kawada T, Nishikawa T, Araki E
  • Journal Title: Biochem Biophys Res Commun Volume: 457 Issue: 1 Pages: 23-20
  • DOI: 10.1016/j.bbrc.2014.12.063
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison of the efficacy of sitagliptin and glimepiride dose-up in Japanese patients with type 2 diabetes poorly controlled by sitagliptin and glimepiride in combination. (2014)
  • Author(s): Shimoda S, Iwashita S, Sekigami T, Furukawa N, Matsuo Y, Ichimori S, Goto R, Maeda T, Watanabe E, Kondo T, Matsumura T, Motoshima H, Nishida K, Araki E
  • Journal Title: J Diabetes Investig Volume: 5 Issue: 3 Pages: 320-326
  • DOI: 10.1111/jdi.12151
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mild electrical stimulation with heat shock reduces visceral adiposity and improves metabolic abnormalities in subjects with metabolic syndrome or type 2 diabetes: Randomized crossover trials. (2014)
  • Author(s): Kondo T, Ono K, Kitano S, Matsuyama R, Goto R, Suico MA, Kawasaki S, Igata M, Kawashima J, Motoshima H, Matsumura T, Kai H, Araki E
  • Journal Title: EBioMedicine Volume: 1 Issue: 1 Pages: 80-89
  • DOI: 10.1016/j.ebiom.2014.11.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of heat shock response in insulin resistance and diabetes. (2014)
  • Author(s): Kondo T, Motoshima H, Igata M, Kawashima J, Matsumura T, Kai H, Araki E
  • Journal Title: Diabetes Metab J Volume: 38 Issue: 2 Pages: 100-1006
  • DOI: 10.4093/dmj.2014.38.2.100
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 高血糖は細胞内低酸素とミトコンドリア由来活性酸素種(mtROS)産生を誘導し、両者の相互作用が糖尿病合併症を進展する. (2015)
  • Author(s): 佐田公紀, 西川武志, 久木留大介, 梶原伸宏, 本島寛之, 松村剛, 荒木栄一
  • Organizer: 第27回分子糖尿病学シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2015-12-05
• [Presentation] インスリン抵抗性および動脈硬化症発症・進展におけるマクロファージ増殖の意義の検討. (2015)
  • Author(s): 瀬ノ口隆文, 山田沙梨恵, 松村剛, 本島寛之, 石井規夫, 福田一起, 村上彩子, 守田雄太郎, 西川武志, 荒木栄一
  • Organizer: 第53回日本糖尿病学会九州地方会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-27
• [Presentation] 従業員の健康増進に、ブルーサークルメニューは有効か？-化血研社員食堂における取組- (2015)
  • Author(s): 毛井順子, 本島寛之, 宮田真理子, 川島隆文, 三島裕子, 前中あおい, 長瀬博美, 吉村沢子, 三浦幸輔, 下村弘之, 猪原淑子, 柿村葉子, 下田誠也, 荒木栄一
  • Organizer: 第53回日本糖尿病学会九州地方会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-27
• [Presentation] 熊本における食環境整備ブルーサークルメニュー開発の新たな展開―社員食堂版の開発― (2015)
  • Author(s): 本島寛之, 柿村葉子, 三浦幸輔, 毛井順子, 村岡まき子, 久木留大介, 三島裕子, 前中あおい, 長瀬博美, 宮田真理子, 川島隆文, 後藤理英子, 吉村沢子, 福田伴美, 猪原淑子, 関上泰二, 白坂亜子, 岸川秀樹, 下田誠也, 荒木栄一
  • Organizer: 第53回日本糖尿病学会九州地方会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-27
• [Presentation] 単鎖脂肪酸の経口摂取はAMPキナーゼ非依存性に内臓脂肪の褐色化（Browning）を誘導する. (2015)
  • 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, 岸川秀樹, 荒木栄一
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Presentation] 熊本におけるブルーサークルメニュー（レストランが提供するヘルシー外食メニュー）開発―臨床効果の評価と普及への道のり―. (2014)
  • Author(s): 本島寛之, 村岡まき子, 高木優樹, 後藤理英子, 下村登貴子, 猪原淑子, 久木留大介, 池田知栄子, 河島淳司, 内田珠美, 澤田真治, 松岡友里, 吉村栄, 山内信吾, 岸川秀樹, 柿村葉子, 荒木栄一
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-05-22 – 2014-05-24