Molecular mechanism of adipose tissue remodeling and lipotoxicity

• Project/Area Number: 20390261
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: OGAWA Yoshihiro Tokyo Medical and Dental University, 難治疾患研究所, 教授 (70291424)
• Co-Investigator(Renkei-kenkyūsha): YASUDA Kazuki 独立行政法人国立国際医療研究センター, 研究所, 部長 (80311611)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2008: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 脂肪組織 / マクロファージ / 炎症 / 肥満 / 遊離脂肪酸 / TRPチャネル / MKP-1 / 飽和脂肪酸 / トランスジェニックマウス / HB-EGF / 脂肪組織リモデリング / MCP-1 / CCR2 / 細胞遊走 / 培養上清 / プロパゲルマニウム

Research Abstract

Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation, suggesting that inflammation may be a potential mechanism, whereby obesity leads to the metabolic syndrome. We have demonstrated that the crosstalk between adipocytes and macrophages may aggravate obesity-induced adipose tissue inflammation. In this study, we provided evidence on the novel molecular mechanisms underlying the inflammatory changes in hypertrophied adipocytes and adipose tissue macrophages, which may lead to novel therapeutic strategies to prevent or treat the metabolic syndrome.

Research Products

• [Journal Article] Unbalanced M1/M2 phenotype of peripheral blood monocytes in obese diabetic patients: effect of pioglitazone. (2010)
  • Author(s): N.Satoh, A.Shimatsu, A.Himeno, Y.Sasaki, H.Yamakage, K.Yamada, T.Suganami, Y.Ogawa.
  • Journal Title: Diabetes Care 33
• [Journal Article] Role of central leptin signaling in renal macrophage infiltration under unilateral ureteral obstruction. (2010)
  • Author(s): M.Tanaka, T.Suganami, S.Sugita, Y.Shimoda, M.Kasahara, S.Aoe, M.Takeya, S.Takeda, Y.Kamei, Y.Ogawa.
  • Journal Title: Endocr.J. 57 Pages: 61-72
• [Journal Article] Insulin-induced ectodomain shedding of heparin-binding epidermal growth factor-like growth factor in adipocytes in vitro : role of a disintegrin and metalloproteinase 17. (2010)
  • Author(s): T.Yamamoto, T.Suganami, M.Kiso-Narita, P.A.Scherle, Y.Kamei, M.Isobe, S.Higashiyama, Y.Ogawa.
  • Journal Title: Obesity 18 Pages: 1888-1894
• [Journal Article] Adipose tissue macrophages : their role in adipose tissue remodeling. (2010)
  • Author(s): T.Suganami, Y.Ogawa.
  • Journal Title: J.Leukoc.Biol. 88 Pages: 33-39
• [Journal Article] Role of transient receptor potential vanilloid 2 in LPS-induced cytokine production in macrophages. (2010)
  • Author(s): K.Yamashiro, T.Sasano, K.Tojo, I.Namekata, J.Kurokawa, N.Sawada, T.Suganami, Y.Kamei, H.Tanaka, N.Tajima, K.Utsunomiya, Y.Ogawa, T.Furukawa.
  • Journal Title: Biochem.Biophys.Res.Commun. 398 Pages: 284-289
• [Journal Article] Anti-obesity effect of eicosapentaenoic acid in high-fat/high-sucrose diet-induced obesity: importance of hepatic lipogenesis. (2010)
  • Author(s): A.Sato, H.Kawano, T.Notsu, M.Ohta, M.Nakakuki, K.Mizuguchi, M.Itoh, T.Suganami, Y.Ogawa.
  • Journal Title: Diabetes 59 Pages: 2495-2504
• [Journal Article] Adipose tissue macrophages : their role in adipose tissue remodeling. (2010)
  • Author(s): T.Suganami, et al.
  • Journal Title: J.Leukoc.Biol. Volume: 88 Pages: 33-39
  • Peer Reviewed
• [Journal Article] Unbalanced M1/M2 phenotype of peripheral blood monocytes in obese diabetic patients : effect of pioglitazone. (2010)
  • Author(s): N.Sato, et al.
  • Journal Title: Diabetes Volume: 33 Pages: 7-7
  • Peer Reviewed
• [Journal Article] Role of transient receptor potential vanilloid 2 in LPS-induced cytokine production in macrophages. (2010)
  • Author(s): K.Yamashiro, et al.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 398 Pages: 284-289
  • Peer Reviewed
• [Journal Article] Role of central leptin signaling in renal macrophage infiltration under unilateral ureteral obstruction. (2010)
  • Author(s): M.Tanaka, et al.
  • Journal Title: Endocrine Journal 57 Pages: 61-72
  • Peer Reviewed
• [Journal Article] Role of central leptin signaling in renal macrophage infiltration under unilateral ureteral obstruction. (2010)
  • Author(s): T.Yamamoto, et al.
  • Journal Title: Obesity (未定, 印刷中)
  • Peer Reviewed
• [Journal Article] Activating transcription factor 3 constitutes a negative feedback mechanism that attenuates saturated fatty acid/Toll-like receptor 4 signaling and macrophage activation in obese adipose tissue. (2009)
  • Author(s): T.Suganami, X.Yuan, Y.Shimoda, K.Uchio-Yamada, N.Nakagawa, I.Shirakawa, T.Usami, T.Tsukahara, K.Nakayama, Y.Miyamoto, K.Yasuda, J.Matsuda, Y.Kamei, S.Kitajima, Y.Ogawa.
  • Journal Title: Circ.Res. 105 Pages: 25-32
• [Journal Article] Highly purified eicosapentaenoic acid reduces cardio-ankle vascular index in association with decrease in serum amyloid A-LDL in metabolic syndrome. (2009)
  • Author(s): N.Satoh, A.Shimatsu, K.Kotani, A.Himeno, H.Yamakage, T.Majima, K.Yamada, T.Suganami, Y.Ogawa.
  • Journal Title: Hypertens.Res. 32 Pages: 1004-1008
  • NAID: 10026124410
• [Journal Article] Activating transcription factor 3 constitutes a negative feedback mechanism that attenuates saturated fatty acid/toll-like receptor 4 signaling and macrophage activation in obese adipose tissue. (2009)
  • Author(s): T.Suganami, et al.
  • Journal Title: Circulation Research 105 Pages: 23-32
  • Peer Reviewed
• [Journal Article] Anti-inflammatory effect of peroxisome proliferator activated receptor α ligands in the interaction between adipocytes and macrophages in obese adipose tissue. (2008)
  • Author(s): T.Toyoda, Y.Kamei, H.Kato, S.Sugita, M.Takeya, T.Suganami, Y.Ogawa.
  • Journal Title: Obesity 16 Pages: 1199-1207
• [Journal Article] for the Japan Obesity and Metabolic Syndrome Study (JOMS) Group.Evaluation of the cardio-ankle vascular index, a new indicator of arterial stiffness independent of blood pressure, in obesity and metabolic syndrome. (2008)
  • Author(s): N.Satoh, A.Shimatsu, Y.Kato, R.Araki, K.Koyama, T.Okajima, M.Tanabe, M.Ooishi, K.Kotani, Y.Ogawa
  • Journal Title: Hypertens.Res. 31 Pages: 1921-1930
• [Journal Article] In vivo and in vitro inhibition of monocyte adhesion to endothelial cells and endothelial adhesion molecules by eicosapentaenoic acid. (2008)
  • Author(s): H.Yamada, M.Yoshida, Y.Nakano, T.Suganami, N.Satoh, T.Mita, K.Azuma, M.Itoh, Y.Yamamoto, Y.Kamei, M.Horie, H.Watada, Y.Ogawa.
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. 28 Pages: 2173-2179
• [Journal Article] Role of C-C chemokine receptor 2 in bone marrow cells in the recruitment of macrophages into obese adipose tissue. (2008)
  • Author(s): A.Ito, T.Suganami, A.Yamauchi, M.Degawa-Yamauchi, M.Tanaka, R.Kouyama, Y.Kobayashi, N.Nitta, K.Yasuda, Y.Hirata, W.A.Kuziel, M.Takeya, S.Kanegasaki, Y.Kamei, Y.Ogawa.
  • Journal Title: J.Biol.Chem. 283 Pages: 35715-35723
• [Journal Article] Role of C-C chemokine receptor 2 in bone marrow cells in the recruitment of macrophages into obese adipose tissue. (2008)
  • Author(s): A. Ito, et al.
  • Journal Title: J. Biol. Chem. 283 Pages: 35715-35723
  • Peer Reviewed
• [Journal Article] In vivo and in vitro inhibition of monocyte adhesion to endothelial cells and endothelial adhesion molecules by eicosapentaenoic acid. (2008)
  • Author(s): H. Yamada, et al.
  • Journal Title: Arterioscler. Thromb. Vase. Biol. 28 Pages: 2173-2179
  • Peer Reviewed
• [Journal Article] Regulation of SREBPlc gene expression in skeletal muscle : role of retinoid X receptor/liver X receptor and forkhead-O1 transcription factor. (2008)
  • Author(s): Y. Kamei, et al.
  • Journal Title: Endocrinology 149 Pages: 2293-2305
  • Peer Reviewed
• [Presentation] 肥満と慢性炎症 (2010)
  • Author(s): 小川佳宏
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 前橋テルサ(前橋市)
  • Year and Date: 2010-10-01
• [Presentation] Activating transcription factor 3 constitutes a negative feedback mechanism that attenuates saturated fatty acid/TLR4 signaling and macrophage activation in obese adipose tissue. (2010)
  • Author(s): T.Suganami, X.Yuan, N.Nakagawa, I.Shirakawa, Y.Kamei, Y.Ogawa
  • Organizer: 2010 Keystone Symposia for the meeting on The Macrophage: Intersection of Pathogenic and Protective Inflammation.
  • Place of Presentation: Banff, Alberta, Canada
• [Presentation] Activating transcription factor 3 constitutes a negative feedback mechanism that attenuates saturated fatty acid/TLR4 signaling and macrophage activation in obese adipose tissue. (2010)
  • Author(s): T.Suganami, X.Yuan, Y.Shimoda, N.Nakagawa, I.Shirakawa, Y.Miyamoto, K.Yasuda, Y.Kamei, S.Kitajima, Y.Ogawa
  • Organizer: 14th International Congress of Endocrinology.
  • Place of Presentation: Kyoto, Japan.
• [Presentation] シンポジウムアピタイトカインの分子基盤と肥満「レプチン」 (2010)
  • Author(s): 田中都、菅波孝祥、小川佳宏
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 前橋
• [Presentation] 新しいNASHモデルとしてのMC4R欠損マウス (2010)
  • Author(s): 伊藤美智子、菅波孝祥、中川信貴、田中都、亀井康富、小川佳宏
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 前橋
• [Presentation] 骨髄Bリンパ球分化に及ぼす中枢レプチン作用 (2010)
  • Author(s): 田中都、菅波孝祥、西條美佐、築地信、亀井康富、小川佳宏
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 前橋
• [Presentation] 肥満の脂肪組織における新たな炎症関連遺伝子の探索 (2010)
  • Author(s): 市岡誠之、菅波孝祥、津田直人、田中都、白川伊吹、平田陽一郎、宮本恵宏、佐田政隆、亀井康富、小川佳宏
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 前橋
• [Presentation] エイコサペンタエン酸の抗肥満作用と抗肝脂肪酸合成作用の関連 (2010)
  • Author(s): 佐藤歩美、伊藤美智子、中久木正則、河野浩之、水口清、菅波孝祥、小川佳宏
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 前橋
• [Presentation] メタボリックシンドロームの基盤病態としての慢性炎症:脂肪組織リモデリングに焦点を当てて (2009)
  • Author(s): 小川佳宏
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-11
• [Presentation] Role of central leptin signaling in renal macrophage infiltration. (2009)
  • Author(s): 田中都, 菅波孝祥, 小川佳宏
  • Organizer: 2009 Keystone Symposia for the meeting on Complications of Diabetes and Obesity.
  • Place of Presentation: Vancouver, British Columbia, Canada.
• [Presentation] 肥満の脂肪組織におけるマクロファージ浸潤の分子機構 (2009)
  • Author(s): 伊藤綾香、菅波孝祥、山内明、山内三爵子、神山隆治、喜田中都、平田結緒、金ケ嵜史朗、亀井康富、小川佳宏
  • Organizer: 第46回日本臨床分子医学会学術集会
  • Place of Presentation: 東京
• [Presentation] 中枢神経系を介するレプチンの炎症調節作用 (2009)
  • Author(s): 田中都、菅波孝祥、杉田聡、竹屋元裕、笠原正登、竹田秀、小川佳宏
  • Organizer: 第82回日本内分泌学会学術総会
  • Place of Presentation: 群馬
• [Presentation] 脂肪細胞特異的MKP-1過剰発現トランスジェニックマウスの作製と表現型の解析 (2009)
  • Author(s): 伊藤綾香、菅波孝祥、袁勲梅、宇佐美貴子、亀井康富、小川佳宏
  • Organizer: 第30回日本肥満学会
  • Place of Presentation: 静岡
• [Presentation] 中枢神経系を介するレプチンの炎症・免疫調節作用 (2009)
  • Author(s): 田中都、菅波孝祥、杉田聡、青江誠一郎、亀井康富、小川佳宏
  • Organizer: 第30回日本肥満学会
  • Place of Presentation: 静岡
• [Presentation] 脂肪組織マクロファージにおける新規炎症抑制性転写因子ATF3の機能的の意義の検討 (2009)
  • Author(s): 中川信貴、菅波孝祥、袁勲梅、白川伊吹、亀井康富、岡淳一郎、小川佳宏
  • Organizer: 第30回日本肥満学会
  • Place of Presentation: 静岡
• [Presentation] ヒトNASH様病変を呈する新しいマウスモデルの確立-MC4R欠損マウスの解析- (2009)
  • Author(s): 伊藤美智子、中川信貴、菅波孝祥、亀井康富、小川佳宏
  • Organizer: 第30回日本肥満学会
  • Place of Presentation: 静岡
• [Presentation] TAXIScanによる肥満脂肪組織へのマクロファージ浸潤機構の解析 (2008)
  • Author(s): 伊藤綾香
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 兵庫
  • Year and Date: 2008-12-09
• [Presentation] 中枢神経系を介するレプチンの炎症調節作用:マウス腎尿細管間質障害モデルを用いて (2008)
  • Author(s): 田中都、菅波孝祥、杉田聡、竹屋元裕、笠原正登、亀井康富、小川佳宏
  • Organizer: 第29回日本肥満学会
  • Place of Presentation: 大分
• [Presentation] 脂肪細胞組織へのマクロファージ浸潤と単球遊走能:リアルタイム細胞動態測定装置を用いた解析 (2008)
  • Author(s): 伊藤綾香、菅波孝祥、田中都、神山隆治、平田結喜緒、亀井康富、小川佳宏
  • Organizer: 第29回日本肥満学会
  • Place of Presentation: 大分
• [Presentation] 脂肪細胞におけるHB-EGF sheddingの分子機構の検討 (2008)
  • Author(s): 山本貴信、菅波孝祥、木曽美奈子、亀井康富、磯部光章、東山繁樹、小川佳宏
  • Organizer: 第29回日本肥満学会
  • Place of Presentation: 大分
• [Presentation] 飽和脂肪酸/TLR4/NFκB経路における新規炎症抑制性転写因子ATF3の機能的意義の検討 (2008)
  • Author(s): 袁勲梅、菅波孝祥、中川信貴、下田百合、北嶋繁孝、小川佳宏
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 兵庫
• [Presentation] TAXIScanによる肥満脂肪組織へのマクロファージ浸潤機構の解析 (2008)
  • Author(s): 伊藤綾香、菅波孝祥、山内明、山内三爵子、神山隆治、田中都、平田結喜緒、金々嵜史朗、亀井康富、小川佳宏
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 兵庫
• [Book] 炎症・再生医学事典(「代謝-糖尿病」) (2009)
  • Author(s): 菅波孝祥、小川佳宏
• [Book] 内科学書Vol.5内分泌疾患代謝・栄養疾患(「脂肪組織由来ホルモン」) (2009)
  • Author(s): 小川佳宏、山崎芳浩
• [Book] アディポネクチンとその受容体抗生活習慣病ホルモンの全貌(「アディポネクチンと炎症」) (2008)
  • Author(s): 伊藤美智子、伊藤綾香、菅波孝祥、小川佳宏
• [Book] 糖尿病学の進歩(「脂肪組織リモデリングの分子機構」) (2008)
  • Author(s): 小川佳宏
• [Remarks] ホームページ等
  • URL: http://www.tmd.ac.jp/mri/prm/index.html
• [Remarks]
  • URL: http://www.tmd.ac.jp/mri/prm/index.html
• [Remarks]
  • URL: http://www.tmd.ac.jp/mri/prm/index.html
• [Remarks]
  • URL: http://www.tmd.ac.jp/mri/prm/index.html