Homeostasis in glycoilipid metabolism-related organs maintained by incretin

• Project/Area Number: 26861554
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Fukuoka University
• Principal Investigator: Yasukochi Tomoyo 福岡大学, 薬学部, 講師 (70507813)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: DOHaD / インクレチン / オステオカルシン / GLP-1 / 生活習慣病

Outline of Final Research Achievements

Maternal diet during pregnancy has been found to influence the health of offspring. However, strategies for modulation of maternal energy metabolism without an adverse effect on the fetus have remained limited.
Under the backgroubnd, this research aimed to investigate the effect of maternal oral administration of uncarboxylated osteocalcin (GluOC), which accelerates GLP-1R signaling and improves metabolic status, on the metabolic status of offspring. As a result, maternal HFS (high-fat, high-sucrose diet) feeding during gestation had deteriorate effects on glucose and lipid parameters, body weight, and adipose tissue inflammation in offspring fed normal diet, and these effects were attenuated by maternal oral GluOC administration. Thus, maternal oral administration of GluOC protects HFS-fed offspring from metabolic disorders induced by maternal obesity.

Research Products

• [Journal Article] Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet (2016)
  • Author(s): Yasutake Y., Mizokami A., Kawakubo-Yasukochi T., Chishaki S., Takahashi I., Takeuchi H., Hirata M.
  • Journal Title: Am. J. Physiol. Endocrinol. Metab. Volume: 310 Issue: 8 Pages: E662-E675
  • DOI: 10.1152/ajpendo.00334.2015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Maternal oral administration of osteocalcin protects offspring from metabolic impairment in adulthood (2016)
  • Author(s): *Kawakubo-Yasukochi T, Kondo A, Mizokami A, Hayashi Y, Chishaki S, Nakamura S, Takeuchi H, Hirata M.
  • Journal Title: Obesity Volume: 24 Issue: 4 Pages: 895-907
  • DOI: 10.1002/oby.21447
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The SQUU-B cell line spread its metastatic properties to nonmetastatic clone SQUU-A from the same patient through exosomes (2016)
  • Author(s): *Kawakubo-Yasukochi T, Morioka M, Hayashi Y, Nishinakagawa T, Hazekawa M, Kawano S, Nakamura S, Nakashima M.
  • Journal Title: J Oral Biosci Volume: 58 Pages: 33-38
  • Peer Reviewed
• [Journal Article] Promotion of insulin-induced glucose uptake in C2C12 myotubes by osteocalcin. (2015)
  • Author(s): Tsuka, S., Aonuma, F., Higashi, S., Ohsumi, T., Nagano, K., Mizokami, A., Kawakubo-Yasukochi, T., Masaki, C., Hosokawa, R. and Hirata, M. and Takeuchi, H.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 459 Issue: 3 Pages: 437-442
  • DOI: 10.1016/j.bbrc.2015.02.123
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Organ network for preventing metabolic syndromes with a reference to the roles of osteocalcin (2015)
  • Author(s): 溝上顕子、*川久保(安河内)友世、竹内弘、平田雅人
  • Journal Title: Folia Pharmacologica Japonica Volume: 145 Issue: 4 Pages: 201-205
  • DOI: 10.1254/fpj.145.201
  • NAID: 130005061556
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed
• [Journal Article] Oral administration of osteocalcin improves glucose utilization by stimulating glucagon-like peptide-1 secretion. (2014)
  • Author(s): Mizokami, A., Yasutake, Y., Higashi, S., Kawakubo-Yasukochi, T., Chishaki, S., Takahashi, I., Takeuchi, H. and Hirata, M.
  • Journal Title: Bone Volume: 69 Pages: 68-79
  • DOI: 10.1016/j.bone.2014.09.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of cathepsin E in decidual macrophage of patients with recurrent miscarriage. (2014)
  • Author(s): Goto S, Ozaki Y, Suzumori N, Yasukochi A, Kawakubo T, Furuno T, Nakanishi M, Yamamoto K, Sugiura-Ogasawara M.
  • Journal Title: Mol Hum Reprod. Volume: 20 Issue: 5 Pages: 454-462
  • DOI: 10.1093/molehr/gau008
  • Peer Reviewed / Open Access
• [Journal Article] A Novel, Potent Dual Inhibitor of Arg-gingipains and Lys-gingipain as a Promising Agent for Periodontal Disease Therapy (2014)
  • Author(s): Kataoka S., Baba A., Suda Y., Takii R., Hashimoto M., *Kawakubo T., Asao T., Kadowaki T., and Yamamoto K.
  • Journal Title: The FASEB J Volume: 28 Issue: 8 Pages: 3564-3578
  • DOI: 10.1096/fj.14-252130
  • Peer Reviewed
• [Journal Article] Cathepsin E in mammary gland: Repression of cathepsin E expression increases the risk of mammary carcinogenesis and links to poor prognosis in breast cancer. (2013)
  • Author(s): Tomoyo Kawakubo, Atsushi Yasukochi, Tatsuya Toyama, Satoru Takahashi, Kuniaki Okamoto, Takayuki Tsukuba, Seiji Nakamura, Yasuhiko Ozaki, Koichi Nishigaki, Hiroko Yamashita, and Kenji Yamamoto
  • Journal Title: Carcinogenesis Volume: 00 Issue: 3 Pages: 1-13
  • DOI: 10.1093/carcin/bgt373
  • Peer Reviewed / Open Access
• [Presentation] Prevention of early atherosclerosis with uncarboxylated osteocalcin (2016)
  • Author(s): Kondo A, *Kawakubo-Yasukochi T, Mizokami A, Takeuchi H, Hirata M.
  • Organizer: The 13th Asia Pacific Federation of Pharmacologist (APFP) Meeting
  • Place of Presentation: Bankok, Thailand
  • Year and Date: 2016-02-01
  • Int'l Joint Research
• [Presentation] Oral squamous carcinoma cell line SQUU-B transfers its metastatic potential to the non-metastatic SQUU-A clone from the same patient through the exosomes (2015)
  • Author(s): *Kawakubo-Yasukochi T, Morioka M, Nishinakagawa T, Hazekawa M, Nakamura S, Nakashima M.
  • Organizer: BMB2015 Biochemistry and Molecular Biology
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
  • Int'l Joint Research
• [Presentation] Research for component in natural products with anti-tumor invasive potential (2015)
  • Author(s): Hazekawa M, Morioka M, Nishinakagawa T, *Yasukochi T, Nakashima M.
  • Organizer: The 74th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] Transmission of invasive potential between oral squamous carcinoma cells from the same patient by the exosomes (2015)
  • Author(s): *Yasukochi T, Morioka M, Nishinakagawa T, Hazekawa M, Nakamura S, Nakashima M.
  • Organizer: The 74th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] Purification and characterization of the cytotoxic factor secreted from cancer cell line (2015)
  • Author(s): Nishinakagawa T, Hazekawa M, *Yasukochi T, Nakashima M.
  • Organizer: The 74th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] 前立腺癌におけるオステオカルシンの位置付け (2015)
  • Author(s): 林 慶和、*川久保-安河内 友世、溝上 顕子、中村 誠司、平田 雅人
  • Organizer: 第13回西日本骨・関節関連疾患懇話会
  • Place of Presentation: 福岡
  • Year and Date: 2015-07-05
  • Int'l Joint Research
• [Presentation] 前立腺癌におけるオステオカルシンの存在意義 (2015)
  • Author(s): 林 慶和、*川久保-安河内 友世、中村 誠司
  • Organizer: 第69回日本口腔科学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-13
  • Int'l Joint Research
• [Presentation] オステオカルシン妊娠期投与による母仔糖脂質代謝の正常化 (2015)
  • Author(s): *川久保-安河内 友世、近藤 皓彦、溝上 顕子、林 慶和、竹内 弘、平田 雅人
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] 前立腺癌におけるオステオカルシンの役割 (2015)
  • Author(s): 林 慶和、*川久保-安河内 友世、溝上 顕子、竹内 弘、平田 雅人
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] 継続的なオステオカルシンの経口投与による糖代謝への影響とその体内動態 (2015)
  • Author(s): 溝上 顕子、安武 雄、東 泉、*川久保-安河内 友世、竹内 弘、平田 雅人
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] 動脈硬化発症機構におけるオステオカルシンの役割 (2014)
  • Author(s): 近藤 皓彦、*川久保-安河内 友世、溝上 顕子、平田 雅人
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] オステオカルシン経口投与時の体内動態と糖代謝への作用 (2014)
  • Author(s): 溝上 顕子、安武 雄、東 泉、*川久保-安河内 友世、高橋 一郎、竹内 弘、平田 雅人
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 超高齢化社会における歯科基礎医学の役割：骨-腸-代謝連関シグナルの解明による全身の健康維持への情報発信 (2014)
  • Author(s): 平田 雅人、溝上 顕子、*川久保-安河内 友世、竹内 弘
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] オステオカルシン妊娠期投与による次世代糖脂質代謝制御の可能性 (2014)
  • Author(s): *川久保-安河内 友世、近藤 皓彦、安武 雄、溝上 顕子、平田 雅人
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] BGM flow (2014)
  • Author(s): Hirata M, Mizokami A, *Kawakubo-Yasukochi T, Otani T, Yasutake Y.
  • Organizer: The 55th International Symposium on Biological Regulation and Enzyme Activity in Normal and Neoplastic Tissues.
  • Place of Presentation: Bologna, Italy
  • Year and Date: 2014-09-16 – 2014-09-17
• [Presentation] オステオカルシンによる母仔糖脂質代謝機構正常化戦略 (2014)
  • Author(s): *川久保-安河内 友世、近藤 皓彦、安武 雄、溝上 顕子、平田 雅人
  • Organizer: 第13回西日本骨・関節関連疾患懇話会
  • Place of Presentation: 福岡
  • Year and Date: 2014-07-05
• [Patent(Industrial Property Rights)] 非または低カルボキシル化オステオカルシンの製造方法およびその利用 (2015)
  • Inventor(s): 平田 雅人
  • Industrial Property Rights Holder: 平田 雅人
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-161238
  • Filing Date: 2015-08-18