Metabolic regulation by adipose tissue macrophage and interleulin-10

• Project/Area Number: 22590971
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: University of Toyama
• Principal Investigator: USUI Isao 富山大学, 大学病院, 講師 (50377272)
• Co-Investigator(Kenkyū-buntansha): TOBE Kazuyuki 富山大学, 大学院・医学薬学研究部(医学), 教授 (30251242)
• Co-Investigator(Renkei-kenkyūsha): MINOKOSHI Yasuhiko 生理学研究所, 発達生理学研究系, 教授 (10200099)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2012: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 内科系臨床医学 / 代謝学 / 脂肪組織 / マクロファージ / メタボリックシンドローム / インターロイキン10

Research Abstract

In this study, we investigated the relationship between adipose tissue M1/M2 macrophages and insulin sensitivity, focusing on the roles of M2 macrophage and interleukin10 （IL-10). Telmisartan, an angiotensin II type I receptor blocker, induced M2 polarity of adipose tissue macrophages with its PPARγ-stimulating activity, while adipose tissue hypoxia induced the M1 polarity. M2 macrophage ablation mice, in which the number of M2 macrophage could be decreased by adding diphtheria toxin, showed smaller adipocyte size and improved insulin sensitivity. The activation of IL-10 signaling in hypothalamus increased the expression of mitochondria-related genes in skeletal muscle and improved inulin sensitivity.

Research Products

• [Journal Article] Adipose tissue hypoxia induces inflammatory M1 polarity of macrophages in an HIF-1α-dependent and HIF-1α-independent manner in obese mice. (2013)
  • Author(s): Fujisaka S, Usui I, Ikutani M, Aminuddin A, Takikawa A, Tsuneyama K, Mahmood A, Goda N, Nagai Y, Takatsu K, Tobe K.
  • Journal Title: Diabetologia Volume: 56(6) Pages: 1403-12
  • Peer Reviewed
• [Journal Article] The Radioprotective 105/MD-1 complex contributes to diet-induced obesity and adipose tissue inflammation (2012)
  • Author(s): Watanabe Y., Nakamura T., Ishikawa S., Fujisaka S., Usui I., Tsuneyama K., Ichihara Y., Wada T., Hirata Y., Suganami T., Izaki H., Akira S., Miyake K., Kanayama H., Shimabukuro M., Sata M., Sasaoka T.,Ogawa Y., Tobe K., Takatsu K., and Nagai Y.
  • Journal Title: Diabetes. Volume: 61(5) Pages: 1199-209
  • Peer Reviewed
• [Journal Article] The Radioprotective 105/MD-1 complex contributes to diet-induced obesity and adipose tissue inflammation (2012)
  • Author(s): Y. Watanabe, T. Nakamura, S. Ishikawa, S. Fujisaka, I. Usui, K. Tsuneyama, Y. Ichihara, T. Wada, Y. Hirata, T. Suganami, H. Izaki, S. Akira, K. Miyake, H. Kanayama, M. Shimabukuro, M. Sata, T. Sasaoka, Y. Ogawa, K. Tobe, K. Takatsu, Y. Nagai
  • Journal Title: Diabetes Volume: 61 Issue: 5 Pages: 1199-1209
  • DOI: 10.2337/db11-1182
  • Peer Reviewed
• [Journal Article] Tobe K. SRT1720, a SIRT1 activator pomotes tumor cell migration, and lung metasiasis of breast cancer in mice (2012)
  • Author(s): Suzuki K
  • Journal Title: Oncol Rep Volume: 27 Pages: 1726-1732
  • DOI: 10.3892/or.2012.1750
  • Peer Reviewed
• [Journal Article] Telmisartan improves insulin resistance and modulates adipose tissue macrophage polarization in high-fat-fed mice (2011)
  • Author(s): Fujisaka S., Usui I., Kanatani Y., Ikutani M., Takasaki I., Tsuneyama K., Tabuchi Y., Bukhari A., Yamazaki Y., Suzuki H., Senda S., Aminuddin A., Nagai Y., Takatsu K., Kobayashi M., To be K.
  • Journal Title: Endocrinology Volume: 152(5) Pages: 1789-99
  • Peer Reviewed
• [Journal Article] Deletion of platelet-derived growth factor receptor-βimproves diabetic nephropathy in Ca2+/calmodulin-dependent protein kinase II α (Thr286 Asp) transgenic mice (2011)
  • Author(s): Suzuki H., Usui I., Kato I., Oya T., Kanatani Y., Yamazaki Y., Fujisaka S., Senda S., Ishii Y., Urakaze M., Mahmood A., Takasawa S., Okamoto H., Kobayashi M., To be K., Sasahara M
  • Journal Title: Diabetologia Volume: 54 Pages: 2953-2962
  • Peer Reviewed
• [Journal Article] Telmisartan Improves Insulin Resistance and Modulates Adipose Tissue Macrophage Polarization in High-Fat-Fed Mice. (2011)
  • Author(s): Fujisaka S, Usui I, Kanatani Y, Ikutani M, Takasaki I, Tsuneyama K, Tabuchi Y, Bukhari A, Yamazaki Y, Suzuki H, Senda S, Aminuddin A, Nagai Y, Takatsu K, Kobayashi M, Tobe K.
  • Journal Title: Endochnology Volume: 152(5) Pages: 1789-1799
  • Peer Reviewed
• [Journal Article] Tumor necrosis factor-alpha accelerates apoptosis of steatotic hepatocytes from amurine model of non-alcoholic fatty liver disease. (2010)
  • Author(s): Zhang W, Kudo H, Kawai K, Fujisaka S, Usui I, Sugiyama T, Tsukada K, Chen N, Takahara T.
  • Journal Title: Biochem Biophys Res Commun Volume: 391(4) Pages: 1731-1736
  • Peer Reviewed
• [Journal Article] Tranlocation of IRS-1 to Cytosol Attenuates Insulin-Stimulated Glucose Transport without Affecting PI3-Kinase Activity (2010)
  • Author(s): Junko Kawahara, Isao Usui, Tetsuro Haruta, Yukiko Kanatani, Kazuyuki Hiratani, Atsuko Takano, Tatsuhito Uno, Minoru Iwata, Masashi Kobayashi, Kazuyuki Tobe
  • Journal Title: The Open Diabctcs Journal Volume: 3 Pages: 14-21
  • Peer Reviewed
• [Presentation] Depletion of CD206-positive cells is associated with increased WAT proliferation and improved insulin sensitivity (2013)
  • Author(s): Aminuddin A., Fujisaka S., Mori H., Kohno K., Usui I., To be K..
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2013-05-17
• [Presentation] 脂肪組織低酸素とインスリン抵抗性 (2013)
  • Author(s): 薄井勲、藤坂志帆、瀧川章子、Arshad Mahmood、戸邉一之
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2013-05-17
• [Presentation] Impact of Adipose Tissue Hypoxia on Macriphage Polarization in Diet-induced Obese Mice. (2012)
  • Author(s): Fujisaka S., Usui I., Ikutani M., Aminuddin A., Senda S., Takikawa A., Ishiki M., Koshimizu Y., Tsuneyama K., Nagai Y., Takatsu K., To be K.
  • Organizer: American Diabetes Association 72nd Scientific Sessions
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2012-06-09
• [Presentation] Myeloid Cell-specific Deletion of SIRT1 Impairs Glucose Metabolism wiht Enhanced Inflammatory Response to Hypoxia (2012)
  • Author(s): Takikawa A., Usui I., Senda S., Fujisaka S., Hattori S., Tsuneyama K., Aminuddin A., Mahmood A., Sasaoka T., Mori H., To be K.
  • Organizer: American Diabetes Association 72nd Scientific Sessions
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2012-06-09
• [Presentation] 慢性炎症とインスリン抵抗性 脂肪組織マクロファージとSIRT1(シンポジウム) (2012)
  • Author(s): 薄井勲,藤坂志帆,瀧川章子,金谷由紀子,戸邉一之
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2012-05-17
• [Presentation] 慢性炎症とインスリン抵抗性 脂肪組織マクロファージとSIRT1 （シンポジウム） (2012)
  • Author(s): 薄井 勲，藤坂志帆，瀧川章子，金谷由紀子，戸邉一之
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Impact of Adipose Tissue Hypoxia on Macriphage Polarization in Diet-induced Obese Mice (2012)
  • Author(s): Fujisaka S., Usui I., Ikutani M., Aminuddin A., Senda S., Takikawa A., Ishiki M., Koshimizu Y., Tsuneyama K., Nagai Y., Takatsu K., Tobe K.
  • Organizer: American Diabetes Association 72nd Scientific Sessions
  • Place of Presentation: Philadelphia(USA)
• [Presentation] Myeloid Cell-specific Deletion of SIRT1 Impairs Glucose Metabolism wiht Enhanced Inflammatory Response to Hypoxia (2012)
  • Author(s): Takikawa A., Usui I., Senda S., Fujisaka S., Hattori S., Tsuneyama K., Aminuddin A., Mahmood A., Sasaoka T., Mori H., Tobe K.
  • Organizer: American Diabetes Association 72nd Scientific Sessions
  • Place of Presentation: Philadelphia(USA)
• [Presentation] Astaxanthin, a Strong Antioxidant, Regulates Insulin Signaling by Various Mechanisms In Vivo (2012)
  • Author(s): Ishiki M., Nishida Y., Fujisaka S., Usui I., Tobe K.
  • Organizer: American Diabetes Association 72nd Scientific Sessions
  • Place of Presentation: Philadelphia(USA)
• [Presentation] 肥満脂肪組織の低酸素がマクロファージの極性に与える影響。(シンポジウム) (2011)
  • Author(s): 薄井勲、戸邉一之
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 兵庫
  • Year and Date: 2011-09-23
• [Presentation] Hyperleptinemia induces leptin resistancce and further worsening obesity (2011)
  • Author(s): Senda S., Inoue A., Suzuki R., Kamei N., Watanabe T., Mahmood A., Takikawa A., Aminuddin A., Fujisaka S., Koshimizu Y., Ishiki M., Usui I., Kadowaki T., To be K.
  • Organizer: American Diabetes Association's 71st Scientific Sessions
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-06-26
• [Presentation] Obesity-induced hypoxia regulates the polarization of adipose tissue macrophages. (2011)
  • Author(s): FujisakaS., UsuiI., Ikutani M., Kanatani Y., Senda S., TakikawaA., Aminuddin, SuzukiH., IshikiM., IwataM., NagaiY., TakatsuK., To be K
  • Organizer: American Diabetes Association's 71st Scientific Sessions
  • Place of Presentation: San Diego, USA
  • Year and Date: 2011-06-26
• [Presentation] Obesity-induced hypoxia regulates the polarization of adipose tissuee macrophages (2011)
  • Author(s): Fujisaka S., Usui I., Ikutani M., Kanatani Y, Senda S., Takikawa A., Aminuddin A., Suzuki H., Ishiki M., Iwata M., Nagai Y., Takatsu K., Tobe K.
  • Organizer: American Diabetes Association 71^<th> Scientific Sessions
  • Place of Presentation: San Diego
  • Year and Date: 2011-06-26
• [Presentation] Hyperleptinemia induces leptin resistancce and further worsening obesity (2011)
  • Author(s): Senda S., Inoue A., Suzuki R., Kamei N., Watanabe T., Mahmood A., Takikawa A., Aminuddin A., Fujisaka S., Koshimizu Y., Ishiki M., Usui I., Kadowaki T., Tobe K.
  • Organizer: American Diabetes Association 71^<th> Scientific Sessions
  • Place of Presentation: San Diego
  • Year and Date: 2011-06-26
• [Presentation] Astaxanthin, a strong antioxidant, possesses various effects on insulin signaling in vitro (2011)
  • Author(s): Ishiki M., Nishida Y., Ishibashi H., Koshimizu Y., Fujisaka S., Usui I., Tobe K.
  • Organizer: American Diabetes Association 71^<th> Scientific Sessions
  • Place of Presentation: San Diego
  • Year and Date: 2011-06-26
• [Presentation] インスリン抵抗性のメカニズムと新しい治療戦略脂肪組織マクロファージとインスリン抵抗性。(シンポジウム) (2011)
  • Author(s): 薄井勲、藤坂志帆、瀧川章子、仙田聡子、小清水由紀子、戸邉一之
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-21
• [Presentation] 低酸素環境に対するM1/M2マクロファージの反応性に関する検討 (2011)
  • Author(s): 藤坂志帆,薄井勲,生谷尚士,仙田聡子,瀧川章子,AminuddinAminuddin,金谷由紀子,長井良憲,石木学,戸邉一之
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-21
• [Presentation] PDGFR-β deletion improves diabetic nephropathy in CaM Kinase IIα (Thr286Asp) Transgenic Mice. (2010)
  • Author(s): Suzuki H., Usui I., Kato I., Kanatani Y., Yamazaki Y., Fujisaka S., Senda S., Urakaze M., Sasahara M., Takasawa S., Okamoto H., Kobayashi M., Tobe K.
  • Organizer: The 70th American Diabetes Association Scientific Sessions
  • Place of Presentation: Orlando
• [Presentation] Activation of interleukin-10 signaling in hypothalamus decreases body weight and improves insulin sensitivity without affecting food intake. (2010)
  • Author(s): Isao Usui, Shiho Fujisaka, Yukiko Kanatani, Agussalim Bukhali, Satoko Senda, Aminuddin, Kazuyuki Tobe
  • Organizer: The 70th American Diabetes Association Scientific Sessions
  • Place of Presentation: Orlando
• [Presentation] The Effect of SRT1720 on Infalammation and Oxidative Stress in White Adipose Tissue of High Fat-fed Mice (2010)
  • Author(s): Yukiko Kanatani, Isao Usui, Shiho Fujisaka, Yuji Matsuya, Satoko Senda, Akiko Takikawa, Aminuddin, Masaharu Urakaze, Kazuyuki Tobe
  • Organizer: American Diabetes Association 70^<th> scientific sessions
  • Place of Presentation: Orlando
• [Presentation] 2型糖尿病のインスリン抵抗性における炎症の役割(学会賞受賞講演) (2010)
  • Author(s): 薄井勲
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
• [Presentation] Regulation of body weight and insulin sensitivity by hypothalamic activation of interleukin-10 signaling(シンポジウム) (2010)
  • Author(s): Isao Usui, Shiho Fujisaka, Yukiko Kanatani, Agussalim Bukhari, Satoko Senda, Aminuddin, Kazuyuki Tobe
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
• [Presentation] 脂肪組織M1/M2マクロファージとインヌリン抵抗性の関連について (2010)
  • Author(s): 藤坂志帆, 薄井勲, アグッサリムブクハリ, 生谷尚士, 金谷由紀子, 山崎夕, 鈴木ひかり, 仙田聡子, 石木学, アミヌディン, 瀧川章子, 浦風雅春, 小林正, 戸辺一之
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
• [Presentation] SIRT1の活性化が肥満マウスの白色脂肪組織の炎症と酸化ストレスに与える影響 (2010)
  • Author(s): 金谷由紀子、薄井勲、藤坂志帆、山崎夕、瀧川章子、鈴木ひかり、仙田聡子、Aminuddin石木学、浦風雅春、戸邉一之
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
• [Book] 最新臨床糖尿病学 上-糖尿病学の最新動向-】糖尿病研究の進歩 インスリン作用およびインスリン抵抗性発現機序 インスリン抵抗性発現の分子機構 インスリン抵抗性における炎症の役割.日本臨床 (2012)
  • Author(s): 薄井勲、戸邉一之
  • Publisher: 日本臨床社
• [Book] 【自然免疫Update-研究最前線】自然免疫の関わる病態と治療への応用 M2マクロファージと疾患.医学のあゆみ (2012)
  • Author(s): 薄井勲、戸邉一之
  • Publisher: 医歯薬出版
• [Book] 脂肪組織におけるマクロファージとインスリン抵抗性.Diabetes Journal (2011)
  • Author(s): 薄井勲、藤坂志帆,戸邉一之
  • Publisher: 協和企画
• [Book] インスリン作用発現とその制御機構.日本臨床 (2011)
  • Author(s): 薄井勲、戸邉一之
  • Publisher: 日本臨床社
• [Book] 2型糖尿病のインスリン抵抗性における炎症の役割.日本臨床 (2011)
  • Author(s): 薄井勲、戸邉一之
  • Publisher: 日本臨床社
• [Book] 脂肪組織でのインスリン作用とインスリン抵抗性.ホルモンと臨床 (2011)
  • Author(s): 薄井勲、戸邉一之
  • Publisher: 医学の世界社