Basic study to unify periodontal medicine and anti-aging medicine

2013 Fiscal Year Final Research Report

• Project/Area Number: 21390556
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Periodontal dentistry
• Research Institution: Hiroshima University ; Kyushu University
• Principal Investigator: NISHIMURA Fusanori 九州大学, 歯学研究院, 教授 (80208222)
• Co-Investigator(Kenkyū-buntansha): ASANO Tomoichiro 広島大学, 大学院医歯薬保健学研究院, 教授 (70242063) ; ABIKO Yoshimitsu 日本大学, 松戸歯学部, 教授 (70050086)
• Project Period (FY): 2009-04-01 – 2014-03-31
• Keywords: 歯周病 / 軽微な慢性炎症 / 脂肪組織 / 炎症細胞 / 耐糖能異常 / 虚血性心疾患リスク

Research Abstract

Periodontal disease is not merely a local infectious disease, but also a low-grade inflammatory disease for the host which may greatly influences glucose tolerance as well as cardiovascular risk. Therefore, our understanding the mechanisms behind this phenomenon at molecular basis is important to establish healthy longevity. Here, we found activated immune cells by periodontal infection migrated into adipose tissues, interacted with adipocytes, thereby enhancing immune responses as well as influencing lipid and glucose metabolism. It is strongly indicataed that the purpose of periodontal treatment is not only to avoid tooth extraction, but also to achieve healthy longevity.

Research Products

• [Journal Article] Improvement of glycated hemoglobin in Japanese subjects with type 2 diabetes by resolution of periodontal inflammation using adjunct topical antibiotics : results from the Hiroshima Study (2013)
  • Author(s): Munenaga Y, The Hiroshima Study Group, Yamashina T, Tanaka J, Nishimura F
  • Journal Title: Diabetes Res Clin Pract Volume: 100 Pages: 53-60
  • DOI: 10.1016/j.diabres.2013.01.028
• [Journal Article] Role of Pin1 in the pathogenesis of non-alcoholic steatohepatitis in a rodent model (2012)
  • Author(s): Nakatsu Y, Otani Y, Sakoda H, Zhang J, Guo Y, Okubo H, Kushiyama A, Fujishiro M, Kikuchi T, Fukushima T, Ohno H, Tsuchiya Y, Kamata H, Nagamachi A, Inaba T, Nishimura F, Katagiri H, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 287 Pages: 44526-44535
  • DOI: 10.1074/jbc.M112.397133
• [Journal Article] Angiotensin receptor 1 blocker valsartan normalizes gene expression profiles of 3T3-L1 adipocytes altered by co-culture with LPS-treated RAW264.7 macrophages (2012)
  • Author(s): Kumamoto S, Kushiyama A, Nakatsu Y, Sakoda H, Fujishiro M, Iwashita M, Ohno H, Zhang J, Guo Y, Aburatani H, Kamata H, Nishimura F, Asano T
  • Journal Title: Obese Res Clin Pract Volume: 6 Pages: e263-346
  • DOI: 10.1016/j.orcp.2012.05.005.263-346
• [Journal Article] Smoking and adipose tissue inflammation suppress leptin expression in Japanese obese males : Potential mechanism of resistance to weight loss among Japanese obese smokers (2012)
  • Author(s): Nagayasu S, Suzuki S, Yamashita A, Taniguchi A, Fukushima M, Nakai Y, Nin K, Watanabe N, Nagasaka S, Yabe D, Nishimura F
  • Journal Title: Tob Induc Dis Volume: 10 Pages: 3
  • DOI: 10.1186/1617-9625-10-3
• [Journal Article] Xanthine oxidoreductase is involved in macrophage foam cell formation and atherosclerosis development (2012)
  • Author(s): Kushiyama A, Okubo H, Sakoda H, Kikuchi T, Fujishiro M, Sato H, Kushiyama S, Iwashita M, Nishimura F, Fukushima T, Nakatsu Y, Kamata H, Kawazu S, Higashi Y, Kurihara H, Asano T
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Pages: 291-298
  • DOI: 10.1161/ATVBAHA.111.234559
• [Journal Article] Adipocyte-macrophage interaction may mediate LPS-induced low-grade inflammation : potential link with metabolic complications (2012)
  • Author(s): Nakarai H, Yamashita A, Nagayasu S, Iwashita M, Kumamoto S, Ohyama H, Hata M, Soga Y, Kushiyama A, Asano T, Abiko Y, Nishimura F
  • Journal Title: Innate Immunity Volume: 18 Pages: 164-170
  • DOI: 10.1177/1753425910393370
• [Journal Article] Smoking, white blood cell counts, and TNF system activity in Japanese male subjects with normal glucose tolerance (2011)
  • Author(s): Watanabe N, Fukushima M, Taniguchi A, Okumura T, Nomura Y, Nishimura F, Aoyama S, Yabe D, Izumi Y, Otsubo R, Nakai Y, Nagasaka S
  • Journal Title: Tob Induc Dis Volume: 9(1) Pages: 12
  • DOI: 10.1186/1617-9625-9-12
• [Journal Article] Valsartan, independently of AT1 receptor or PPARγ, suppresses LPS-induced macrophage activation and improves insulin resistance in co-cultured adipocytes (2011)
  • Author(s): Iwashita M, Sakoda H, Kushiyama A, Fujishiro M, Ohno H, Nakatsu Y, Fukushima T, Kumamoto S, Tsuchiya Y, Kikuchi T, Kurihara H, Akazawa H, Komuro I, Kamata H, Nishimura F, Asano T
  • Journal Title: Am J Physiol - Endocrinol Metab Volume: 302 Pages: E286-296
  • DOI: 10.1152/ajpendo.00324.2011
• [Journal Article] Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with IRS-1 and enhances insulin actions and adipogenesis (2011)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Zhang J, Ono H, Fujishiro M, Kikuchi T, Fukushima T, Yoneda M, Ohno H, Horike N, Kanna M, Tsuchiya Y, Kamata H, Nishimura F, Isobe T, Ogihara T, Katagiri H, Oka Y, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 286 Pages: 20812-20822
  • DOI: 10.1074/jbc.M110.206904
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity (2011)
  • Author(s): Ohno H, Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Otani Y, Okubo H, Yoneda M, Fukushima T, Kamata H, Nishimura F, Kurihara H, Katagiri H, Oka Y, Asano T
  • Journal Title: Am J Physiol-Cell Physiol Volume: 300 Pages: C1047-1054
  • DOI: 10.1152/ajpcell.00416
• [Journal Article] Periodontal disease and hyper-triglyceridemia in Japanese subjects : potential association with enhanced lipolysis (2011)
  • Author(s): Nakarai H, Yamashita A, Takagi M, Adachi M, Sugiyama M, Noda H, Katano M, Yamakawa R, Nakayama K, Takumiya H, Nakai Y, Taniguchi A, Nishimura F
  • Journal Title: Metabolism Volume: 60 Pages: 823-829
  • DOI: 10.1016/j.metabol.2010.07.034
• [Journal Article] Pin1 associates with and induces translocation of CRTC2 to the cytosol, thereby suppressing CRE transcriptional activity (2010)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Horike N, Yoneda M, Ohno H, Kamata H, Tahara H, Isobe T, Nishimura F, Katagiri H, Oka Y, Fukushima T, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 285 Pages: 33018-33027
  • DOI: 10.1074/jbc.M110.137836
• [Journal Article] Decreased SIRT1 expression and LKB1 phosphorylation occur with long-term high-fat diet feeding, in addition to AMPK phosphorylation impairment in the early phase (2010)
  • Author(s): Yoneda M, Guo Y, Ono H, Nakatsu Y, Zhang J, Cui XL, Iwashita M, Kumamoto S, Tsuchiya Y, Sakoda H, Fujishiro M, Kushiyama A, Koketsu Y, Kikuchi T, Kamata H, Nishimura F, Asano T
  • Journal Title: Obese Res Clin Pract Volume: 4 Pages: e201-e207
  • DOI: 10.1016/j.orcp.2010.02.002
• [Journal Article] Macrophage foam cell formation is augmented in serum from patients with diabetic angiopathy (2010)
  • Author(s): Cui X, Kushiyama A, Yoneda M, Nakatsu Y, Guo Y, Zhang J, Ono H, Kanna M, Sakoda H, Ono H, Kikuchi T, Fujishiro M, Shiomi M, Kamata H, Kurihara H, Kikuchi M, Kawazu S, Nishimura F, Asano T
  • Journal Title: Diabetes Res Clin Pract Volume: 87 Pages: 57-63
  • DOI: 10.1016/j.diabres.2009.10.011
• [Journal Article] Periodontal conditions in Werner syndrome (2010)
  • Author(s): Nishimura F, Arakawa M, Goto M
  • Journal Title: J Periodontol Volume: 81 Pages: 3
  • DOI: 10.1902/jop.2009.090461
• [Presentation] The periodontal host response with type 2 diabetes (2013)
  • Author(s): Nishimura F
  • Organizer: 第8回グローバルCOE国際シンポジウムMolecular Science in Oral-Systemic Medicine-Winter Seminar-
  • Place of Presentation: 東京医科歯科大学,Tokyo
  • Year and Date: 20130203-04
• [Presentation] 歯周病と糖尿病の関連性からひもとくOral-Systemic Medicineの分子基盤(日本学術会議シンポジウム高齢社会におけるOral-systemic medicine) (2013)
  • Author(s): 西村英紀
  • Organizer: 第55回歯科基礎医学会学術大会・総会
  • Place of Presentation: 岡山
  • Year and Date: 2013-09-21
• [Presentation] 歯周病と糖尿病の関連性からひもとくOral-Systemic Medicineの分子基盤(ワークショップ11口腔内炎症性疾患と全身の連関:Oral-Systemic Medicineの新たな展開) (2013)
  • Author(s): 西村英紀
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2013-06-07
• [Presentation] New therapeutic concept against severe periodontitis in type 2 diabetic subjects. Lunch &Learning 32 (2012)
  • Author(s): Nishimura F
  • Organizer: 90^<th> General Session of International Association for Dental Research
  • Place of Presentation: Iguacu Falls, Brazil
  • Year and Date: 20120620-23
• [Presentation] Key note lecture - Periodontal Disease : More than sixth complication of diabetes mellitus (2012)
  • Author(s): Nishimura F
  • Organizer: 9^<th> IDF-WPR Congress 4^<th> AASD Scientific Meeting(in Symposium"Diabetes and Periodontal Disease")
  • Place of Presentation: Kyoto
  • Year and Date: 2012-11-25
• [Presentation] The periodontal host response with type 2 diabetes (2011)
  • Author(s): Nishimura F
  • Organizer: 24^<th> Indonesian Dentist Association Congress
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 20110401-02
• [Book] 「代謝・内分泌疾患診療 最新ガイドライン」糖尿病と歯周病 (2012)
  • Author(s): 西村英紀, 門脇孝、下村伊一郎編(共著)
  • Total Pages: 104-106
  • Publisher: 総合医学社
• [Book] 「糖尿病の療養指導2011」糖尿病の危険因子としての歯周病 (2011)
  • Author(s): 西村英紀, 日本糖尿病学会編(共著)
  • Total Pages: 96-99
  • Publisher: 診断と治療社
• [Book] VI.糖尿病の治療-4-心血管リスク管理における糖尿病合併症治療-13歯周病, 門脇孝総編集, 植木浩二郎, 小田原雅人, 佐倉宏, 浜野久美子, 松田昌文, 森保道編集「心血管リスクを防ぐ糖尿病診療ガイド」(共著) (2011)
  • Author(s): 西村英紀
  • Total Pages: 369-375
  • Publisher: 南山堂
• [Book] 「科学的根拠に基づく糖尿病診療ガイドライン2010」11.糖尿病と歯周病 (2010)
  • Author(s): 河野隆幸, 西村英紀, 日本糖尿病学会編集
  • Total Pages: 127-134
  • Publisher: 南光堂