脂肪酸伸長酵素Elovl6欠損マウスにおけるショ糖嗜好性亢進機序の解明
Publicly Offered Research
Project Area | Molecular Basis and Disorders of Control of Apetite and Fat Accumulation |
Project/Area Number |
25126701
|
Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
|
Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
|
Research Institution | University of Tsukuba |
Principal Investigator |
島野 仁 筑波大学, 医学医療系, 教授 (20251241)
|
Project Period (FY) |
2013-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
|
Keywords | 脂肪酸 / 脳 / 食欲 / 嗜好性 |
Outline of Annual Research Achievements |
我々は、脂肪酸伸長酵素Elovl6のクローニングおよびノックアウトマウスの解析から、それまで予想されていなかった脂肪酸の質と生活習慣病の関連を明らかにしてきた。さらに、Elovl6欠損マウスはショ糖に対する嗜好性が亢進することを見出した。本研究では、Elovl6欠損マウスのショ糖嗜好性の亢進の要因、特にその脳内機構について解析し、肥満を誘導するような嗜好性に基づいた摂食亢進や、ストレスに起因した嗜好性食品の過食(気晴らし喰い障害)のような摂食障害の分子基盤の解明に貢献することを目的とした。 本年度は、摂食や嗜好性に関与する様々な神経ペプチや受容体に対するアゴニストあるいはアンタゴニストの投与がElovl6欠損マウスのショ糖嗜好性におよぼす影響を解析した。その結果、Elovl6欠損マウスのショ糖嗜好性の亢進をほぼキャンセルさせる化合物を見出した。この化合物の標的受容体は複数のアイソフォームをもつため、その中でどのアイソフォームが重要であるか検討している。さらに、Elovl6欠損によりこの受容体が活性化する分子メカニズムと、ショ糖嗜好性の亢進に寄与する脳部位の特定を現在進めている。
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Research Progress Status |
26年度が最終年度であるため、記入しない。
|
Strategy for Future Research Activity |
26年度が最終年度であるため、記入しない。
|
Report
(2 results)
Research Products
(22 results)
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[Journal Article] Ligand-activated PPARα-dependent DNA demethylation regulates the fatty acid β-oxidation genes in the postnatal liver.2014
Author(s)
Ehara T, Kamei Y, Yuan X, Takahashi M, Kanai S, Tamura E, Tsujimoto K, Tamiya T, Nakagawa Y, Shimano H, Takai-Igarashi T, Hatada I, Suganami T, Hashimoto K, Ogawa Y.
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Journal Title
Diabetes.
Volume: 64(3)
Issue: 3
Pages: 775-84
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Hepatic CREB3L3 Controls Whole-Body Energy Homeostasis and Improves Obesity and Diabetes2014
Author(s)
Yoshimi Nakagawa,* Aoi Satoh,* Sachiko Yabe,* Mika Furusawa, Naoko Tokushige, Hitomi Tezuka, Motoki Mikami, Wakiko Iwata, Akiko Shingyouchi, Takashi Matsuzaka, Shiori Kiwata, Yuri Fujimoto, Yasushi Kawakami, Osamu Urayama, Nobuhiro Yamada, and Hitoshi Shimano et. al
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Journal Title
Endocrinology
Volume: 155(12)
Issue: 12
Pages: 4706-4719
DOI
Related Report
Peer Reviewed
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[Journal Article] Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced impairment of insulin secretion.2014
Author(s)
Tang N, Matsuzaka T, Suzuki M, Nakano Y, Zao H, Yokoo T, Suzuki-Kemuriyama N, Kuba M, Okajima Y, Takeuchi Y, Kobayashi K, Iwasaki H, Yatoh S, Takahashi A, Suzuki H, Sone H, Shimada M, Nakagawa Y, Yahagi N, Yamada N, Shimano H.
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Journal Title
Biochem Biophys Res Commun.
Volume: 450(1)
Issue: 1
Pages: 318-23
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo.2014
Author(s)
Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Nakazeki F, Ide Y, Koyama S, Sowa N, Yahagi N, Shimano H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K.
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Journal Title
Scientific Reports
Volume: 4
Issue: 1
Pages: 5312-5312
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] MafB promotes atherosclerosis by inhibiting foam-cell apoptosis2014
Author(s)
Hamada M, Nakamura M, Tran MT, Moriguchi T, Hong C, Ohsumi T, Dinh TT, Kusakabe M, Hattori M, Katsumata T, Arai S, Nakashima K, Kudo T, Kuroda E, Wu CH, Kao PH, Sakai M, Shimano H, Miyazaki T, Tontonz P, Takahashi S
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Journal Title
Nat Commun
Volume: 5
Issue: 1
Pages: 3147-3147
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Estrogen receptor ligands ameliorate fatty liver through a nonclassical estrogen receptor/Liver X receptor pathway in mice.2014
Author(s)
Han SI, Komatsu Y, Murayama A, Steffensen KR, Nakagawa Y, Nakajima Y, Suzuki M, Oie S, Parini P, Vedin LL, Kishimoto H, Shimano H, Gustafsson JÅ, Yanagisawa J.
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Journal Title
Hepatology
Volume: 59(5)
Issue: 5
Pages: 1791-1802
DOI
Related Report
Peer Reviewed
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[Journal Article] MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice.2013
Author(s)
Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Sowa N, Yahagi N, Shimano H, Matsumura S, Inoue K, Marusawa H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K
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Journal Title
Nat Commun.
Volume: 4:2883
Issue: 1
Pages: 2883-2883
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP1c Tg mice fed high-fat and high-fructose diet2013
Author(s)
Wada T, Miyashita Y, Sasaki M, Aruga Y, Nakamura Y, Ishii Y, Sasahara M, Kanasaki K, Kitada M, Koya D, Shimano H, Tsuneki H, Sasaoka
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Journal Title
Am J Physiol Endocrinol Metab
Volume: 305
Issue: 11
Pages: E1415-E1425
DOI
Related Report
Peer Reviewed
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[Journal Article] Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization.2013
Author(s)
Izumida Y, Yahagi N, Takeuchi Y, Nishi M, Shikama A, Takarada A, Masuda Y, Kubota M, Matsuzaka T, Nakagawa Y, Iizuka Y, Itaka K, Kataoka K, Shioda S, Niijima A, Yamada T, Katagiri H, Nagai R, Yamada N, Kadowaki T, Shimano H
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Journal Title
Nat Commun.
Volume: 4
Issue: 1
Pages: 2316-2316
DOI
Related Report
Peer Reviewed / Open Access
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