The molecular mechanism of organ metabolic disease state and abnormal brain function caused by Elovl6-mediated qualitative changes of fatty acids
Project/Area Number |
15H02541
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | University of Tsukuba |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
松坂 賢 筑波大学, 医学医療系, 准教授 (70400679)
中川 嘉 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80361351)
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥41,470,000 (Direct Cost: ¥31,900,000、Indirect Cost: ¥9,570,000)
Fiscal Year 2017: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2016: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2015: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
|
Keywords | 脂肪酸伸長酵素 / 脂肪毒性 / インスリン抵抗性 / 糖尿病 / 脳 / 生活習慣病 / 高次脳機能 / 脂質 / 脳・神経 / 脂肪酸 |
Outline of Final Research Achievements |
Liver-specific Elovl6 KO mice showed enhanced hepatic insulin signaling when they were fed high-sucrose diet or were crossed with ob/ob mice. Through transcriptome and lipidomics analysis, we identified and characterized gene X and lipid Y as hepatic insulin signaling regulators. To define the role of Elovl6 in type 2 diabetes development, we assessed the effects of Elovl6 deletion in leptin receptor-deficient C57BL/KsJ db/db mice. The db/db-Elovl6 KO mice had a markedly increased β-cell mass with increased proliferation and decreased apoptosis, an adaptive increase in insulin, and improved glycemic control. Elovl6 is a fundamental factor linking dysregulated lipid metabolism to β-cell dysfunction, islet inflammation, and β-cell apoptosis in diabetes. Moreover, we found the crucial role of Elovl6 in neural stem cell function and found the key lipid that regulate neural stem cell function.
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Report
(4 results)
Research Products
(58 results)
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[Journal Article] Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood2018
Author(s)
X Yuan, K Tsujimoto, K Hashimoto, K Kawahori, N Hanzawa, M Hamaguchi, T Seki, M Nawa, T Ehara, Y Kitamura, I Hatada, M Konishi, N Itoh, Y Nakagawa, H Shimano, T Takai-Igarashi, Y Kamei, Y Ogawa.
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Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 636-636
DOI
Related Report
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[Journal Article] A candidate functional SNP rs7074440 in TCF7L2 alters gene expression through C-FOS in hepatocytes.2018
Author(s)
Piao X, Yahagi N, Takeuchi Y, Aita Y, Murayama Y, Sawada Y, Shikama A, Masuda Y, Nishi-Tatsumi M, Kubota M, Izumida Y, Sekiya M, Matsuzaka T, Nakagawa Y, Sugano Y, Iwasaki H, Kobayashi K, Yatoh S, Suzuki H, Yagyu H, Kawakami Y, Shimano H.
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Journal Title
FEBS Lett.
Volume: 592(3)
Issue: 3
Pages: 422-433
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[Journal Article] Novel non-alcoholic steatohepatitis model with histopathological and insulin-resistant features.2018
Author(s)
Owada Y, Tamura T, Tanoi T, Ozawa Y, Shimizu Y, Hisakura K, Matsuzaka T, Shimano H, Nakano N, Sakashita S, Matsukawa T, Isoda H, Ohkohchi N.
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Journal Title
Pathol Int.
Volume: 68(1)
Issue: 1
Pages: 12-22
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NAID
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Peer Reviewed
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[Journal Article] Role of Hormone-sensitive Lipase in Leptin-Promoted Fat Loss and Glucose Lowering2017
Author(s)
Takanashi M, Taira Y, Okazaki S, Takase S, Kimura T, Li CC, Xu PF, Noda A, Sakata I, Kumagai H, Ikeda Y, Iizuka Y, Yahagi N, Shimano H, Osuga JI, Ishibashi S, Kadowaki T, Okazaki H
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 24
Issue: 11
Pages: 1105-1116
DOI
NAID
ISSN
1340-3478, 1880-3873
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Peer Reviewed
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[Journal Article] A key role of nuclear factor Y in the refeeding response of fatty acid synthase in adipocytes.2017
Author(s)
Nishi-Tatsumi M, Yahagi N, Takeuchi Y, Toya N, Takarada A, Murayama Y, Aita Y, Sawada Y, Piao X, Oya Y, Shikama A, Masuda Y, Kubota M, Izumida Y, Matsuzaka T, Nakagawa Y, Sekiya M, Iizuka Y, Kawakami Y, Kadowaki T, Yamada N, Shimano H.
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Journal Title
FEBS Lett
Volume: 591
Issue: 7
Pages: 965-978
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism.2017
Author(s)
Oishi Y, Spann NJ, Link VM, Muse ED, Strid T, Edillor C, Kolar MJ, Matsuzaka T, Hayakawa S, Tao J, Kaikkonen MU, Carlin AF, Lam MT, Manabe I, Shimano H, Saghatelian A, Glass CK.
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Journal Title
Cell Metab.
Volume: 25(2)
Issue: 2
Pages: 412-427
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα.2016
Author(s)
Nakagawa Y, Satoh A, Tezuka H, Han SI, Takei K, Iwasaki H, Yatoh S, Yahagi N, Suzuki H, Iwasaki Y, Sone H, Matsuzaka T, Yamada N, Shimano H.
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Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 39182-39182
DOI
NAID
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Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducing Npc1l1 expression.2016
Author(s)
Kikuchi T, Orihara K, Oikawa F, Han SI, Kuba M, Okuda K, Satoh A, Osaki Y, Takeuchi Y, Aita Y, Matsuzaka T, Iwasaki H, Yatoh S, Sekiya M, Yahagi N, Suzuki H, Sone H, Nakagawa Y, Yamada N, Shimano H.
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Journal Title
Mol Metab.
Volume: 5(11)
Pages: 1092-1102
NAID
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[Journal Article] KLF15 Enables Rapid Switching between Lipogenesis and Gluconeogenesis during Fasting.2016
Author(s)
Takeuchi Y, Yahagi N, Aita Y, Murayama Y, Sawada Y, Piao X, Toya N, Oya Y, Shikama A, Takarada A, Masuda Y, Nishi M, Kubota M, Izumida Y, Yamamoto T, Sekiya M, Matsuzaka T, Nakagawa Y, Urayama O, Kawakami Y, Iizuka Y, Gotoda T, Itaka K, Kataoka K, Nagai R, Kadowaki T, Yamada N, Lu Y, Jain MK, and Shimano H
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Journal Title
Cell Rep.
Volume: 16
Issue: 9
Pages: 2373-2386
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Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice.2016
Author(s)
Suzuki-Kemuriyama N, Matsuzaka T, Kuba M, Ohno H, Han SI, Takeuchi Y, Isaka M, Kobayashi K, Iwasaki H, Yatoh S, Suzuki H, Miyajima K, Nakae D, Yahagi N, Nakagawa Y, Sone H, Yamada N, Shimano H.
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Journal Title
PLoS One.
Volume: 11(6)
Issue: 6
Pages: e0157580-e0157580
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NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system.2016
Author(s)
Nakagawa Y, Oikawa F, Ohno H, Yagishita Y, Satoh A, Osaki Y, Takei K, Kikuchi T, Song-iee H, Mizuno S. Matsuzaka T, Iwasaki H, Kobayashi K, Yatoh S, Yahagi N, Suzuki H, Sone H, Takahashi S, Yamada N, Shimano H.
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Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 27857-27857
DOI
NAID
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[Journal Article] In Search of the Ideal Resistance Training Program to Improve Glycemic Control and its Indication for Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.2016
Author(s)
Ishiguro H, Kodama S, Horikawa C, Fujihara K, Hirose AS, Hirasawa R, Yachi Y, Ohara N, Shimano H, Hanyu O, Sone H.
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Journal Title
Sports Med.
Volume: 46(1):67-77.
Issue: 1
Pages: 67-77
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[Journal Article] Meta-analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus2016
Author(s)
Kodama S, Fujihara K, Ishiguro H, Horikawa C, Ohara N, Yachi Y, Tanaka S, Shimano H, Kato K, Hanyu O, Sone H
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Journal Title
Diabetes/metabolism research and reviews
Volume: 32
Issue: 2
Pages: 178-186
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[Journal Article] Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.2015
Author(s)
Osaki Y, Nakagawa Y, Miyahara S, Iwasaki H, Ishii A, Matsuzaka T, Kobayashi K, Yatoh S, Takahashi A, Yahagi N, Suzuki H, Sone H, Ohashi K, Ishibashi S, Yamada N, Shimano H
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Journal Title
Biochem Biophys Res Commun.
Volume: 466(3)
Issue: 3
Pages: 536-540
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[Journal Article] Identification of human ELOVL5 enhancer regions controlled by SREBP.2015
Author(s)
Shikama A, Shinozaki H, Takeuchi Y, Matsuzaka T, Aita Y, Murayama T, Sawada Y, Piao X, Toya N, Oya Y, Takarada A, Masuda Y, Nishi M, Kubota M, Izumida Y, Nakagawa Y, Iwasaki H, Kobayashi K, Yatoh S, Suzuki H, Yagyu H, Kawakami Y, Yamada N, Shimano H, Yahagi N.
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Journal Title
Biochem Biophys Res Commun.
Volume: 465(4)
Issue: 4
Pages: 857-63
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[Journal Article] A common genetic variant of the chromogranin A-derived peptide catestatin is associated with atherogenesis and hypertension in a Japanese population2015
Author(s)
Choi Y, Miura M, Nakata Y, Sugasawa T, Nissato S, Otsuki T, Sugawara J, Iemitsu M, Kawakami Y, Shimano H, Iijima Y, Tanaka K, Kuno S, Allu PK, Mahapatra NR, Maeda S, Takekoshi K.
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Journal Title
Endocrine Journal
Volume: 62
Issue: 9
Pages: 797-804
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ISSN
0918-8959, 1348-4540
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[Journal Article] Circulating Malondialdehyde-Modified LDL-Related Variables and Coronary Artery Stenosis in Asymptomatic Patients with Type 2 Diabetes2015
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Fujihara K, Suzuki H, Sato A, Kodama S, Heianza Y, Saito K, Iwasaki H, Kobayashi K, Yatoh S, Takahashi A, Yahagi N, Yagyu H, Sone H, Shimano H.
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Volume: 印刷中
Pages: 507245-507245
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