Role of the ventromedial hypothalamus in the regulation of food intake and metabolism.

• Project/Area Number: 24390058
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: MINOKOSHI Yasuhiko 生理学研究所, 発達生理学研究系, 教授 (10200099)
• Co-Investigator(Renkei-kenkyūsha): OKAMOTO Shiki 生理学研究所, 発達生理学研究系, 助教 (40342919) ; TODA Chitoku 生理学研究所, 発達生理学研究系, 特別協力研究員 (70571199)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
• Keywords: 視床下部 / 代謝 / 摂食 / レプチン / DREADD

Outline of Final Research Achievements

We examined the role of the ventromedial hypothalamic (VMH) neuron in the control of metabolism in mice by using Hyperinsulinemic-euglycemic clamp and 2DG method. We also examined the effect of preferential activation of Ad4BP neuron in the VMH on food intake and metabolism. Leptin increased glucose uptake in muscle and inhibited glucose production in the liver by enhancing insulin sensitivity. Activation of Ad4BP neuron in the VMH by DREADD inhibited food intake and increased insulin sensitivity in skeletal muscle and the liver. These results thus suggested that VMH neurons play an important role in insulin sensitivity in skeletal muscle and the liver as well as food intake.

Research Products

• [Journal Article] Conditional ablation of orexin/hypocretin neurons : A new mouse model for the study of narcolepsy and orexin system function. (2014)
  • Author(s): Tabuchi S, Tsunematsu T, Black SW, Tominaga M, Maruyama M, Takagi K, Minokoshi Y, Sakurai T, Kilduff TS, Yamanaka A
  • Journal Title: The Joumal of Neuroscience Volume: (in press) Issue: 19 Pages: 6495-6509
  • DOI: 10.1523/jneurosci.0073-14.2014
  • Peer Reviewed / Open Access
• [Journal Article] Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice. (2014)
  • Author(s): Sasaki T, Kikuchi O, Shimpuku M, Susanti VY, Yokota-Hashimoto H, Taguchi R, Shibusawa N, Sato T, Tang L, Amano K, Kitazumi T, Kuroko M, Fujita Y, Maruyama J, Lee YS, Kobayashi M, Nakagawa T, Minokoshi Y, Harada A, Yamada M, Kitamura T.
  • Journal Title: Diabetologia Volume: 57 Issue: 4 Pages: 819-831
  • DOI: 10.1007/s00125-013-3140-5
  • Peer Reviewed / Open Access
• [Journal Article] Enhancement of leptin receptor signaling by SOCS3 deficiency induces development of gastric tumors in mice. (2014)
  • Author(s): Inagaki-Ohara K, Mayuzumi H, Kato S, Minokoshi Y, Otsubo T, Kawamura YI, Dohi T, Matsuzaki G, Yoshimura A.
  • Journal Title: Oncogene Volume: 33 Issue: 1 Pages: 74-84
  • DOI: 10.1038/onc.2012.540
  • Peer Reviewed / Open Access
• [Journal Article] 視床下部研究の進歩 (2014)
  • Author(s): 箕越靖彦
  • Journal Title: 日本臨床増刊号 最新肥満症学 Volume: 72 Pages: 109-114
• [Journal Article] 視床下部と骨格筋におけるAMPKの代謝調節作用 (2014)
  • Author(s): 箕越靖彦
  • Journal Title: 医学のあゆみ Volume: 250 Pages: 766-772
• [Journal Article] 血糖値制御 (2014)
  • Author(s): 箕越靖彦
  • Journal Title: Clinical Neuroscience Volume: 32 Pages: 1379-1382
• [Journal Article] Leptin, GABA, and glucose control. (2013)
  • Author(s): Kahn BB, Minokoshi Y
  • Journal Title: Cell Metabolism Volume: 18 Issue: 3 Pages: 304-306
  • DOI: 10.1016/j.cmet.2013.08.015
  • Peer Reviewed
• [Journal Article] Extracellular signal-regulated kinase in the ventromedial hypothalamus mediates leptin-induced glucose uptake in red-type skeletal muscle. (2013)
  • Author(s): Toda C, Shiuchi T, Kageyama H, Okamoto S, Coutinho EA, Sato T, Okamatsu-Ogura Y, Yokota S, Takagi K, Tang L, Saito K, Shioda S, Minokoshi Y.
  • Journal Title: Diabetes Volume: 62 Issue: 7 Pages: 2295-2307
  • DOI: 10.2337/db12-1629
  • Peer Reviewed
• [Journal Article] 中枢神経系とエネルギー代謝調節 (2013)
  • Author(s): 箕越 靖彦
  • Journal Title: 実験医学 増刊号 Volume: 31 Pages: 3251-3256
• [Journal Article] 視床下部による糖・脂質代謝調節 (2013)
  • Author(s): 箕越 靖彦
  • Journal Title: BIO Clinica Volume: 28 Pages: 49-54
• [Journal Article] Extracellular Signal-Regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-Induced Glucose Uptake in Red-Type Skeletal Muscle. (2013)
  • Author(s): Chitoku Toda, et al.
  • Journal Title: Diabetes Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle. (2012)
  • Author(s): Minokoshi Y
  • Journal Title: Indian J Endocrinol Metab Volume: 16 Issue: 9 Pages: 562-562
  • DOI: 10.4103/2230-8210.105573
  • Peer Reviewed
• [Presentation] 視床下部による骨格筋への代謝調節作用 (2014)
  • Author(s): 箕越靖彦
  • Organizer: 第41回日本神経内分泌学会学術集会
  • Place of Presentation: 都道府県会館、千代田区、東京
  • Year and Date: 2014-10-31 – 2014-11-02
  • Invited
• [Presentation] Leptin enhances insulin-induced glucose uptake in skeletal muscle via MEK/ERK signaling in the ventromedial hypothalamus. (2014)
  • Author(s): Yasuhiko Minokoshi, Chitoku Toda
  • Organizer: 2014 Asia-Pacific Diabetes and Obesity Study Group
  • Place of Presentation: Grand Hilton Seoul, Seoul, South Korea
  • Year and Date: 2014-05-16 – 2014-05-17
  • Invited
• [Presentation] Role of the ventromedial hypothalamus in leptin-induced glucose metabolic regulation in skeletal muscle and the liver. (2014)
  • Author(s): Minokoshi Y, Toda C
  • Organizer: The 91st Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Kagoshima University, Kagoshima
  • Invited
• [Presentation] 視床下部AMPKによる摂食調節機構 (2012)
  • Author(s): 箕越靖彦
  • Organizer: 第1回糖尿病治療の新時代～基礎と臨床を学ぶ～
  • Place of Presentation: ウェスティンホテル大阪、大阪市、大阪府(招待講演)
  • Year and Date: 2012-07-06
• [Presentation] レプチンは視床下部腹内側核において異なるシグナル伝達因子を介して骨格筋および肝臓のインスリン感受性を調節する。 (2012)
  • Author(s): 戸田知得, 他
  • Organizer: 第85回日本内分泌学会
  • Place of Presentation: 名古屋国際会議場、名古屋市、愛知県
• [Book] 糖尿病の分子標的と治療薬辞典 (2013)
  • Author(s): 箕越 靖彦
  • Total Pages: 342
  • Publisher: 羊土社
• [Remarks] 自然科学研究機構 生理学研究所 生殖・内分泌系発達機構研究部門
  • URL: https://www.nips.ac.jp/endoclin/
• [Remarks] 生理学研究所 生殖・内分泌系発達機構
  • URL: http://www.nips.ac.jp/endoclin/
• [Remarks] 生理学研究所
  • URL: http://www.nips.ac.jp/
• [Remarks]
  • URL: http://www.nips.ac.jp/endoclin/