Elucidation of the role of hypothalamic Sirt1 in energy balance regulation.

• Project/Area Number: 23790270
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Gunma University
• Principal Investigator: SASAKI Tsutomu 群馬大学, 生体調節研究所, 准教授 (50466687)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 視床下部 / Sirt1 / 摂食調節 / エネルギー消費 / 交感神経 / 褐色脂肪 / sirtuin / 摂食

Research Abstract

In order to address the role of Sirt1, an NAD^+-dependent deacetylase, in regulating energy balance, we analyzed POMC or AgRP Sirt1 conditional knock-in mice. We found that Sirt1 in POMC neurons stimulates energy expenditure through sympathetic nervous system while Sirt1 in AgRP neurons suppresses food intake, thereby negatively regulating energy balance. Meanwhile we found that diet-induced obesity suppresses the function of hypothalamic Sirt1 and promotes positive energy balance.

Research Products

• [Presentation] 視床下部弓状核のSirt1はエネルギーバランスを負に制御する (2013)
  • Author(s): 佐々木努、新福摩弓、菊池司、ビナヤンティスサンティ、橋本博美、小林雅樹、北村忠弘
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台
  • Year and Date: 2013-04-25
• [Presentation] Hypothalamic Sirt1 overexpression leads to a negative energy balance (2013)
  • Author(s): Sasaki T, Shimpuku M, Kikuchi O, Susanti VY, Yokota-Hashimoto H, Kobayashi M, Kitamura T
  • Organizer: The 90th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 東京
  • Year and Date: 2013-03-27
• [Presentation] Hypothalamic Sirt1 achieves negative energy balance by stimulating energy expenditure in POMC neurons and by suppressing food intake in AgRP neurons (2013)
  • Author(s): Sasaki T, Kitamura T
  • Organizer: Keystone Symposium "Neuronal Control of Appetite, Metabolism and Weight"
  • Place of Presentation: Banff, Alberta(カナダ)
  • Year and Date: 2013-03-20
• [Presentation] Hypothalamic Sirt1 achieves negative energy balance by stimulating energy expenditure in POMC neurons and by suppressing food intake in AgRP neurons (2012)
  • Author(s): Tsutomu Sasaki, Mayumi Shimpuku, Osamu Kikuchi, Vina Yanti Susanti, Hiromi Yokota-Hashimoto, Masaki Kobayashi, Tadahiro Kitamura
  • Organizer: Keystone Symposia on Aging and Diseases of Aging
  • Place of Presentation: 東京
  • Year and Date: 2012-10-25
• [Presentation] POMC・AgRPニューロンでのSirt1過剰発現マウスの摂食・エネルギー消費調節機構 (2012)
  • Author(s): 佐々木努、新福摩弓、菊池司、橋本博美、小林雅樹、北村忠弘
  • Organizer: 第33回日本肥満学会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-11
• [Presentation] 視床下部Sirt1による抗肥満効果の分子メカニズム (2012)
  • Author(s): 佐々木努、新福摩弓、菊池司、天野剛介、北住知也、橋本博美、小林雅樹、北村忠弘
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-18
• [Presentation] POMC・AgRPニューロンでのSirt1過剰発現マウスの摂食・エネルギー消費調節機構 (2012)
  • Author(s): 佐々木努、新福摩弓、菊池司、橋本博美、小林雅樹、北村忠弘
  • Organizer: 第55回日本糖尿病学会
  • Place of Presentation: 横浜
  • Year and Date: 2012-05-19
• [Presentation] POMC・AgRPニューロンでのSirt1過剰発現マウスの摂食・エネルギー消費調節機構 (2012)
  • Author(s): 佐々木努、新福摩弓、菊池司、橋本博美、小林雅樹、北村忠弘
  • Organizer: 第85回日本内分泌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-04-19
• [Presentation] Induction of Sirt1 expression in the murine hypothalamic AgRP and Pomc neurons leads to lean phenotype due to decreased food intake and increased energy expenditure (2012)
  • Author(s): Sasaki T, Shimpuku M, Kikuchi O, Yokota-Hashimoto H, Kobayashi M, Kitamura T
  • Organizer: The 89th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 松本市(長野県)
  • Year and Date: 2012-03-29
• [Presentation] Induction of Sirt1 expression in the murine hypothalamic AgRP and Pomc neurons leads to lean phenotype due to decreased food intake and increased energy expenditure (2012)
  • Author(s): Sasaki T, Kitazumi T, Amano K, Kikuchi O, Shimpuku M, Yokota-Hashimoto H, Kobayashi M, Kitamura T
  • Organizer: Keystone Symposium "Sirtuins in Metabolism, Aging and Disease"
  • Place of Presentation: Tahoe City, California(米国)
  • Year and Date: 2012-02-14
• [Presentation] Conditional Knock-in of SIRT1 in AGRP or POMC Neurons Lead to Lean Phenotype due to Decreased Food Intake and Increased Energy Expenditure (2011)
  • Author(s): Tsutomu Sasaki, Tadahiro Kitamura
  • Organizer: American Diabetes Association Research Symposium "Diabetes and the Brain"
  • Place of Presentation: Alexandria, Virginia(米国)
  • Year and Date: 2011-10-30
• [Presentation] AgRP・PomcニューロンでのSirt1過剰発現マウスでの摂食・エネルギー消費調節機構 (2011)
  • Author(s): 佐々木努、北住知也、天野剛介、菊池司、橋本博美、小林雅樹、北村忠弘
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 淡路島(兵庫)
  • Year and Date: 2011-09-24
• [Presentation] Induction of Sirt1 expression in the murine hypothalamic AgRP and Pomc neurons leads to lean phenotype due to decreased food intake and increased energy expenditure (2011)
  • Author(s): Tsutomu Sasaki, Tomoya Kitazumi, Kosuke Amano, Osamu Kikuchi, Hiromi Yokota-Hashimoto, Masaki Kobayashi, Tadahiro Kitamura
  • Organizer: The 34th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-15
• [Presentation] Pomc-Cre; Sirt1 conditional Knock-In Mice Present Lean Phenotype Due to Increased Energy Expenditure (2011)
  • Author(s): Tsutomu Sasaki, Kosuke Amano, Tomoya Kitazumi, Osamu Kikuchi, Masaki Kobayashi, Tadahiro Kitamura
  • Organizer: American Diabetes Association 71st Scientific Sessions
  • Place of Presentation: San Diego, California(米国)
  • Year and Date: 2011-06-26
• [Presentation] POMC陽性神経細胞のSirt1はエネルギー消費を制御する (2011)
  • Author(s): 佐々木努、天野剛介、北住知也、菊池司、小林雅樹、北村忠弘
  • Organizer: 第54回日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] Rosa26-Sirt1ノックインマウスを用いた視床下部Sirt1とエネルギーバランスの解析 (2011)
  • Author(s): 佐々木努、天野剛介、北住知也、菊池司、小林雅樹、北村忠弘
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2011-04-23
• [Presentation] POMC・AgRPニューロンでのSirt1過剰発現マウスの摂食・エネルギー消費調節機構
  • Author(s): 佐々木努
  • Organizer: 第８５回日本内分泌学会
  • Place of Presentation: 名古屋
• [Presentation] POMC・AgRP ニューロンでのSirt1 過剰発現マウスの摂食・エネルギー消費調節機構
  • Author(s): 佐々木努
  • Organizer: 第５５回日本糖尿病学会
  • Place of Presentation: 横浜
• [Presentation] 視床下部Sirt1による抗肥満効果の分子メカニズム
  • Author(s): 佐々木努
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] POMC・AgRPニューロンでのSirt1過剰発現マウスの摂食・エネルギー消費調節機構
  • Author(s): 佐々木努
  • Organizer: 第３３回日本肥満学会
  • Place of Presentation: 京都
• [Presentation] Hypothalamic Sirt1 achieves negative energy balance by stimulating energy expenditure in POMC neurons and by suppressing food intake in AgRP neurons
  • Author(s): 佐々木努
  • Organizer: Keystone Symposia on Aging and Diseases of Aging
  • Place of Presentation: 東京
• [Presentation] Hypothalamic Sirt1 overexpression leads to a negative energy balance
  • Author(s): 佐々木努
  • Organizer: 第９０回日本生理学会
  • Place of Presentation: 東京
• [Presentation] Hypothalamic Sirt1 achieves negative energy balance by stimulating energy expenditure in POMC neurons and by suppressing food intake in AgRP neurons.
  • Author(s): 佐々木努
  • Organizer: Keystone Symposium “Neuronal Control of Appetite, Metabolism and Weight”
  • Place of Presentation: Banff, Canada
• [Presentation] 視床下部弓状核のSirt1はエネルギーバランスを負に制御する
  • Author(s): 佐々木努
  • Organizer: 第８６回日本内分泌学会
  • Place of Presentation: 仙台
• [Presentation] POMC陽性神経細胞のSirt1はエネルギー消費を制御する
  • Author(s): 佐々木 努、天野 剛介、北住 知也、菊池 司、小林 雅樹、北村 忠弘
  • Organizer: 第５４回日本糖尿病学会
  • Place of Presentation: 札幌
• [Presentation] Pomc-Cre; Sirt1 conditional Knock-In Mice
  • Author(s): 佐々木 努、天野 剛介、北住 知也、菊池 司、小林 雅樹、北村 忠弘
  • Organizer: アメリカ糖尿用学会71st Scientific Sessions
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Sirt1 expression in AgRP and Pomc neurons
  • Author(s): 佐々木努、北住知也、天野剛介、菊池司、橋本博美、小林雅樹、北村忠弘
  • Organizer: Japan Neuroscience Society
  • Place of Presentation: 横浜
• [Presentation] AgRP・PomcニューロンでのSirt1過剰発現マウスでの摂食・エネルギー消費調節機構
  • Author(s): 佐々木努、北住知也、天野剛介、菊池司、橋本博美、小林雅樹、北村忠弘
  • Organizer: 第３２回日本肥満学会
  • Place of Presentation: 淡路島
• [Presentation] Conditional Knock-in of SIRT1 in AGRP or POMC
  • Author(s): Tsutomu Sasaki, Tadahiro Kitamura
  • Organizer: ADA Research Symposium "Diabetes and the Brain"
  • Place of Presentation: Alexandria, Virginia, USA
• [Presentation] Conditional Knock-in of SIRT1 in AGRP or POMC
  • Author(s): 佐々木努、北住知也、天野剛介、菊池司、新福摩弓、橋本博美、小林雅樹、北村忠弘
  • Organizer: キーストンシンポジウム
  • Place of Presentation: Tahoe City, California, USA
• [Presentation] Conditional Knock-in of SIRT1 in AGRP or POMC
  • Author(s): 佐々木努、新福摩弓、菊池司、橋本博美、小林雅樹、北村忠弘
  • Organizer: 第８９回日本生理学会
  • Place of Presentation: 松本