Effects of exercise training on inflammaging: the role of macrophages in the molecular mechanisms

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590752
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene
• Research Institution: Kyorin University
• Principal Investigator: KIZAKI Takako 杏林大学, 医学部, 教授 (00322446)
• Co-Investigator(Renkei-kenkyūsha): OHNO Hideki 杏林大学, 医学部, 教授 (00133819)
• Project Period (FY): 2011 – 2013
• Keywords: マクロファージ / 炎症反応 / 老化 / 運動トレーニング / グレリン / 時計遺伝子

Research Abstract

Exercise training prevented the infiltration of inflammatory macrophages to adipose tissue and exerted anti-inflammatory effects for obesity-related chronic inflammation. Expression of ghrelin, which exerts potent anti-inflammatory effects, in peritoneal marophages was decreased by obesity and recovered by exercise training, suggesting that exercise training suppresses obesity-induced inflammation through ghrelin. On the other hand, a circadian clock gene Rev-erb modulates the inflammatory function of macrophages through the direct regulation of a chemokine Ccl2 expression. Overexpression of Rev-erb in murine macrophage cell line RAW264 cells suppressed the induction of Ccl2 following a LPS endotoxin challenge, resulting in impaired the activity of cell adhesion and migration. These data suggest that Rev-erb regulates the inflammatory infiltration of macrophages through the suppression of Ccl2 expression and participates in aging- or obesity-associated inflammation.

Research Products

• [Journal Article] A circadian clock gene, Rev-erbα, modulates the inflammatory function of macrophages through the egative regulation of Ccl2 expression (2014)
  • Author(s): Sato, S., Sakurai, T., Ogasawara, J., Takahashi, M., Izawa, T., Imaizumi, K., Taniguchi, N., Ohno, H. and Kizaki, T
  • Journal Title: J. Immunol Volume: 192 Pages: 407-417
  • DOI: 10.4049/jimmunol.1301982
  • Peer Reviewed
• [Journal Article] ETAS, an enzyme-treated asparagus extract, attenuates amyloidβ-induced cellular disorder in PC12 cells (2014)
  • Author(s): Ogasawara, J., Ito, T., Wakame, K., Kitadate, K., Sakurai, T., Sato, S., Ishibashi, Y., Izawa, T., Takahashi, K., Ishida, H., Takabatake, I., Kizaki, T. and Ohno, H
  • Journal Title: Nat. Prod. Commun Volume: 9 Pages: 561-564
  • Peer Reviewed
• [Journal Article] Enzyme-treated Asparagus officinalis extract shows neuroprotective effects and attenuates cognitive impairment in senescence- accelerated mice (2014)
  • Author(s): Sakurai, T., Ito, T., Wakame, K., Kitadate, K., Arai, T., Ogasawara, J., Kizaki, T., Sato, S., Ishibashi, Y., Fujiwara, T., Akagawa, K., Ishida, H. and Ohno, H
  • Journal Title: Nat. Prod. Commun Volume: 9 Pages: 101-106
  • Peer Reviewed
• [Journal Article] Intracellularβ2-adrenergic receptor signaling specificity in mouse skeletal muscle in response to single-doseβ2-agonist clenbuterol treatment and acute exercise (2013)
  • Author(s): Sato, S., Shirato, K., Mitsuhashi, R., Inoue, D., Kizaki, T., Ohno, H., Tachiyashiki, K. and Imaizumi, K
  • Journal Title: J. Physiol. Sci Volume: 63 Pages: 211-218
  • DOI: 10.1007/s12576-013-0253-z
  • Peer Reviewed
• [Journal Article] Oligomerised lychee fruit-derived polyphenol attenuates cognitive impairment in senescence-accelerated mice and endoplasmic reticulum stress in neuronal cells (2013)
  • Author(s): Sakurai, T., Kitadate, K., Nishioka, H., Fujii, H., Ogasawara, J., Kizaki, T., Sato, S., Fujiwara, T., Akagawa, K., Izawa, T. and Ohno, H
  • Journal Title: Br. J. Nutr Volume: 110 Pages: 1549-1558
  • DOI: 10.1017/S000711451300086X
  • Peer Reviewed
• [Journal Article] The Effects of Exercise Training on Obesity-Induced Dysregulated Expression of Adipokines in White Adipose Tissue (2013)
  • Author(s): Sakurai, T., Ogasawara, J., Kizaki, T., Sato S, Ishibashi Y, Takahashi M, Kobayashi, O., Oh-Ishi, S., Nagasawa, J., Takahashi, K., Ishida, H., Izawa, T. and Ohno, H
  • Journal Title: Int. J. Endocrinol Volume: 2013 Pages: 801743
  • DOI: 10.1155/2013/801743
  • Peer Reviewed
• [Journal Article] Exercise and oxidative stress in hypoxia (2013)
  • Author(s): Nagasawa, J., Kizaki, T. and Ohno, H
  • Journal Title: J. Phys. Fit. Sports Med Volume: 2 Pages: 481-486
  • DOI: 10.7600/jpfsm.2.481
  • Peer Reviewed
• [Journal Article] Copy number variations due to large genomic deletion in X-linked chronic granulomatous disease (2012)
  • Author(s): Arai, T., Oh-ishi, T., Yamamoto, H., Nunoi, H, Kamizono, J., Uehara, M., Kubota, T., Sakurai, T., Kizaki, T. and Ohno, H
  • Journal Title: PLoS One Volume: 7 Pages: e27782
  • DOI: 10.1371/journal.pone.0027782
• [Journal Article] Effect of exercise on HIF-1 and VEGF signaling (2012)
  • Author(s): Ohno, H., Shirato, K., Sakurai, T., Ogasawara, J., Sumitani, Y., Sato, S., Imaizumi, K., Ishida, H. and Kizaki, T
  • Journal Title: J. Phys. Fit. Sports Med Volume: 1 Pages: 5-16
  • DOI: 10.7600/jpfsm.1.5
  • Peer Reviewed
• [Journal Article] The effects of exercise on macrophage function (2012)
  • Author(s): Kizaki, T., Sato, S., Sakurai, T., Ogasawara, J., Imaizumi, K., Izawa, T., Nagasawa, J., Saitoh, D., Haga, S. and Ohno, H
  • Journal Title: J. Phys. Fit. Sports Med Volume: 1 Pages: 113-124
  • DOI: 10.7600/jpfsm.1.113
  • Peer Reviewed
• [Journal Article] Effects ofβ_2 - agonists and exercise onβ_2 - adrenergic receptor signaling in skeletal muscles (2012)
  • Author(s): Sato, S., Shirato, K., Kizaki, T., Ohno, H., Tachiyashiki, K. and Imaizumi, K
  • Journal Title: J. Phys. Fit. Sports Med Volume: 1 Pages: 139-144
  • DOI: 10.7600/jpfsm.1.139
  • Peer Reviewed
• [Journal Article] Effects of exercise on the hexosamine biosynthetic pathway and glycosylation (2012)
  • Author(s): Shirato, K., Kizaki, T., Ohno, H. and Imaizumi, K
  • Journal Title: J. Phys. Fit. Sports Med Volume: 1 Pages: 145-150
  • DOI: 10.7600/jpfsm.1.145
  • Peer Reviewed
• [Journal Article] Higher Levels of ATGL Are Associated with Exercise-Induced Enhancement of Lipolysis in Rat Epididymal Adipocytes (2012)
  • Author(s): Ogasawara, J., Sakurai, T., Kizaki, T., Ishibashi, Y., Izawa, T., Sumitani, Y., Ishida, H., Radak, Z., Haga, S. and Ohno, H
  • Journal Title: PLoS One Volume: 7 Pages: e40876
  • DOI: 10.1371/journal.pone.0040876
  • Peer Reviewed
• [Journal Article] Oligonol-induced Degradation of Perilipin 1 is Regulated through Lysosomal Degradation Machinery (2012)
  • Author(s): Ogasawara, J., Kitadate, K., Nishioka, H., Fujii, H., Sakurai, T., Kizaki, T., Izawa, T., Ishida, H. and Ohno, H
  • Journal Title: Nat. Prod. Commun Volume: 7 Pages: 1193-1196
  • Peer Reviewed
• [Journal Article] Effect of physical exercise on lipolysis in white adipocytes (2012)
  • Author(s): Ogasawara, J., Sakurai, T., Kizaki, T., Takahashi, K., Sumitani, Y., Ishida, H., Izawa, T., Toshinai, K., Nakano, N. and Ohno, H
  • Journal Title: J. Phys. Fit. Sports Med Volume: 1 Pages: 351-356
  • DOI: 10.7600/jpfsm.1.351
  • Peer Reviewed
• [Journal Article] Exercise training and the promotion of neurogenesis and neurite outgrowth in the hippocampus (2012)
  • Author(s): Sakurai, T., Ogasawara, J., Kizaki, T., Ishibashi, Y., Fujiwara, T., Akagawa, K., Izawa, T., Radák, Z. and Ohno, H
  • Journal Title: J. Phys. Fit. Sports Med Volume: 1 Pages: 333-338
  • DOI: 10.7600/jpfsm.1.333
  • Peer Reviewed
• [Journal Article] Recent advances in the adaptations of adipose tissue to physical activity : Morphology and adipose tissue cellularity (2012)
  • Author(s): Izawa, T., Ogasawara, J., Sakurai, T., Nomura, S., Kizaki, T. and Ohno, H
  • Journal Title: J. Phys. Fit. Sports Med Volume: 1 Pages: 381-387
  • DOI: 10.7600/jpfsm.1.381
  • Peer Reviewed
• [Journal Article] Comparison of the effect of oligonol, a new lychee fruit-derived low molecular form of polyphenol, and epigallocatechin-3-gallate on lipolysis in rat primary adipocytes (2011)
  • Author(s): Ogasawara, J., Kitadate, K., Nishioka, H., Fujii, H., Sakurai, T., Kizaki, T., Izawa, T., Ishida, H. and Ohno, H
  • Journal Title: Phytother. Res Volume: 250 Pages: 467-471
  • DOI: 10.1002/ptr.3296
  • Peer Reviewed
• [Journal Article] Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages (2011)
  • Author(s): Kizaki, T., Maegawa, T., Sakurai, T., Ogasawara, J., Ookawara, T., Oh-ishi, S., Izawa, T., Haga, S. and Ohno, H
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 413 Pages: 454-459
  • DOI: 10.1016/j.bbrc.2011.08.117
  • Peer Reviewed
• [Journal Article] Involvement of leucine zipper transcription factor-like protein (Lztfl1) in the attenuation of cognitive impaiament by exercise training. (2011)
  • Author(s): Sakurai, T., Ogasawara, J., Kizaki, T., Ishibashi, Y., Fujiwara, T., Akagawa, K., Izawa, T., Oh-ishi, S., Haga, S. and Ohno, H
  • Journal Title: Biochem Biophys. Res. Commun Volume: 416 Pages: 125-129
  • DOI: 10.1016/j.bbrc.2011.11.008
  • Peer Reviewed
• [Presentation] シンポジウム"脂肪蓄積と代謝異常に対する運動の効果―動物実験で得られた知見のヒトへの応用―":運動と脂肪細胞の働き (2014)
  • Author(s): 小笠原準悦, 櫻井拓也, 石橋義永, 木崎節子, 白土健, 今泉和彦, 井澤鉄也, 大野秀樹
  • Organizer: 第160回日本体力医学会関東地方会
  • Place of Presentation: 調布
  • Year and Date: 2014-03-08
• [Presentation] A circadian clock gene Rev-erbαmodulates inflammatory functions of macrophages through negative regulation of monocyte chemoattractant protein-1 expression (2013)
  • Author(s): Kizaki, T., Sato, S. and Ohno, H
  • Organizer: 第42回日本免疫学会学術総会
  • Place of Presentation: 幕張
  • Year and Date: 2013-12-11
• [Presentation] 時計遺伝子Rev-erbαはMCP1遺伝子の発現を抑制しマクロファージ免疫機能を制御する (2013)
  • Author(s): 佐藤章悟, 木崎節子, 櫻井拓也, 小笠原準悦, 石橋義永, 長澤純一, 桜井智野風, 井澤鉄也, 今泉和彦, 芳賀脩光, 大野秀樹
  • Organizer: 第68回日本体力医学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-09-21
• [Presentation] 水泳運動は前駆細胞からの褐色脂肪細胞化を促す (2013)
  • Author(s): 小笠原準悦, 櫻井拓也, 木崎節子, 佐藤章悟, 石橋義永, 井澤鉄也, 宮崎裕美, 斎藤大蔵, 十枝内厚次, 大石修司, 芳賀脩光, 大野秀樹
  • Organizer: 第68回日本体力医学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-09-21
• [Presentation] Inhibitory effect of ETAS against amyloid beta-induced cellular disorder in PC12 cells (2013)
  • Author(s): Ogasawara, J., Ito, T., Takanari, J., Sakurai, T., Kizaki, T., Sato, S., Ishibashi, Y., Nagasawa, J., Saito, D., Nakano, N., Izawa, T. and Ohno, H
  • Organizer: 21^<st> International Congress on Nutrition and Integrative Medicine
  • Place of Presentation: Sapporo
  • Year and Date: 2013-07-27
• [Presentation] 運動は肥満による脂肪組織の線維化関連因子の発現増加を減弱させる (2013)
  • Author(s): 櫻井拓也, 小笠原準悦, 木崎節子, 長澤純一, 芳賀脩光, 大野秀樹
  • Organizer: 第21回日本運動生理学会大会
  • Place of Presentation: 川越
  • Year and Date: 2013-07-27
• [Presentation] 持久性走トレーニングによる白色脂肪細胞の脂肪分解反応の亢進にはATGLの発現変化が関与する (2013)
  • Author(s): 小笠原準悦, 櫻井拓也, 佐藤章悟, 石橋義永, 長澤純一, 大石修司, 芳賀脩光, 井澤鉄也, 木崎節子, 大野秀樹
  • Organizer: 第158回日本体力医学会関東地方会
  • Place of Presentation: 新座
  • Year and Date: 2013-07-13
• [Presentation] 水泳運動により誘導される肩甲骨周囲骨格筋群の褐色脂肪細胞化の検討 (2013)
  • Author(s): 小笠原準悦, 櫻井拓也, 木崎節子, 佐藤章悟, 石橋義永, 井澤鉄也, 斎藤大蔵, 大石修司, 芳賀脩光, 大野秀樹
  • Organizer: 第83回日本衛生学会学術総会
  • Place of Presentation: 金沢
  • Year and Date: 2013-03-25
• [Presentation] The enzyme-treated Asparagus offcinalis extract shows anti-stress effects in neuronal cells and prevents cognitive impairment in senescense-accelerated mice (2012)
  • Author(s): Sakurai, T., Kitadate, K., Nishioka, H., Wakame, K., Fujii, H., Ogasawara, J., Kizaki, T., Sato, S., Ishibashi, Y., Fujiwara, T., Akagawa, K., Imaizumi, K., Saitoh, D., Izawa, T. and Ohno, H
  • Organizer: The 6th International Niigata Simposium on Diet and Health
  • Place of Presentation: Niigata
  • Year and Date: 2012-10-17
• [Presentation] 運動は肥満による脂肪組織のデルマトポンチン発現増加を減弱させる (2012)
  • Author(s): 櫻井拓也, 小笠原準悦, 木崎節子, 佐藤章悟, 井澤鉄也, 芳賀脩光, 今泉和彦, 大石修司, 大野秀樹
  • Organizer: 第67回日本体力医学会大会
  • Place of Presentation: 岐阜
  • Year and Date: 2012-09-15
• [Presentation] 水泳運動は骨格筋前駆細胞から褐色脂肪細胞への分化を促進する (2012)
  • Author(s): 小笠原準悦, 櫻井拓也, 木崎節子, 井澤鉄也, 武政徹, 芳賀脩光, 長澤純一, 大野秀樹
  • Organizer: 第20回日本運動生理学会大会
  • Place of Presentation: つくば
  • Year and Date: 2012-07-29
• [Presentation] The extract from stems of Asparagus offcinalis enhances the expression of heat shock proteins and shows anti-stress effects in neural cells (2012)
  • Author(s): Sakurai, T., Kitadate, K., Nishioka, H., Wakame, K., Fujii, H., Ogasawara, J. Kizaki, T., Sato, S., Ishibashi, Y., Imaizumi, K., Saitoh, D., Izawa, T. and Ohno, H
  • Organizer: The 20th Internathional Congress on Nutrition and Integrative Medicine
  • Place of Presentation: Sapporo
  • Year and Date: 2012-07-22
• [Presentation] 水泳運動は骨格筋前駆細胞から褐色脂肪細胞への分化シグナルを促進する (2012)
  • Author(s): 小笠原準悦, 櫻井拓也, 木崎節子, 石橋義永, 炭谷由計, 井澤鉄也, 石田均, 鈴木健二, 芳賀脩光, 大野秀樹
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-25
• [Presentation] Preventive effects of Oligonol on cognitive impairment in senescence-accelerated mice and identification on its molecular target in hippocampus (2011)
  • Author(s): Sakurai, T., Kitadate, K., Nishioka, H., Wakame, K., Ogasawara, J., Kizaki, T., Ishibashi, Y., Fujiwara, T., Akagawa, K., Nakano, N., Izawa, T. and Ohno, H
  • Organizer: The 19th International Congress on Nutrition and Integrative Medicine
  • Place of Presentation: Sapporo
  • Year and Date: 2011-10-16
• [Presentation] 骨格筋から褐色脂肪細胞への分化機構に及ぼす寒冷曝露と水泳運動の効果 (2011)
  • Author(s): 小笠原準悦, 櫻井拓也, 木崎節子, 石橋義永, 住谷由計, 井澤鉄也, 宮崎裕美, 大石修司, 芳賀脩光, 大野秀樹
  • Organizer: 第66回日本体力医学会大会
  • Place of Presentation: 下関
  • Year and Date: 2011-09-17
• [Presentation] 運動は老化促進モデルマウスの認知機能障害を予防する (2011)
  • Author(s): 櫻井拓也, 小笠原準悦, 木崎節子, 井澤鉄也, 長澤純一, 芳賀脩光, 大野秀樹
  • Organizer: 第19回日本運動生理学会大会
  • Place of Presentation: 徳島
  • Year and Date: 2011-08-26
• [Book] 身体の活性酸素消去を高める方法, 活性酸素の本当の姿 (2014)
  • Author(s): 大野秀樹, 木崎節子 (鈴木敬一郎編)
  • Total Pages: 149-169
  • Publisher: (有)ナップ
• [Book] マクロファージは褐色脂肪組織に燃料を補給する, ここまでわかった燃える褐色脂肪の不思議 (2013)
  • Author(s): 木崎節子, 佐藤章悟, 大河原知水 (斎藤昌之, 大野秀樹編)
  • Total Pages: 56
  • Publisher: (有)ナップ
• [Book] UCP2は活性酸素を制御する, ここまでわかった燃える褐色脂肪の不思議 (2013)
  • Author(s): 木崎節子, 鈴木健二, 芳賀脩光 (斎藤昌之, 大野秀樹編)
  • Total Pages: 100
  • Publisher: (有)ナップ
• [Book] 水泳は褐色脂肪組織のグッド・ストレッサー, ここまでわかった燃える褐色脂肪の不思議 (2013)
  • Author(s): 大野秀樹, 上野伸正, 木崎節子 (斎藤昌之, 大野秀樹編)
  • Total Pages: 150
  • Publisher: (有)ナップ
• [Book] 第23章燃焼系素材と運動, 機能性食品素材と運動療法-生活習慣病予防と運動機能維持向上を目指して- (2012)
  • Author(s): 大野秀樹, 櫻井拓也, 小笠原準悦, 石橋義永, 木崎節子 (大澤俊彦, 佐藤祐造監修)
  • Total Pages: 177-184
  • Publisher: 大阪シーエムシー出版
• [Book] エネルギースタンドとしての脂肪組織, 脂肪組織のエクササイズバイオロジー一冊まるごと脂肪組織と運動の話 (2011)
  • Author(s): 小笠原準悦, 木崎節子, 石橋義永, 芳賀脩光, 大野秀樹 (井澤鉄也, 駒林隆夫編)
  • Total Pages: 23-70
  • Publisher: (有)ナップ
• [Book] 内分泌器官としての脂肪組織:アデイポカインの分泌, 脂肪組織のエクササイズバイオロジー一冊まるごと脂肪組織と運動の話 (2011)
  • Author(s): 櫻井拓也, 小笠原準悦, 木崎節子, 炭谷由計, 石田均, 大野秀樹 (井澤鉄也, 駒林隆夫編)
  • Total Pages: 71-130
  • Publisher: (有)ナップ