2013 Fiscal Year Final Research Report
Identification of novel mechanisms in obesity development.
| Project/Area Number |
23591293
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Tohoku University |
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Principal Investigator |
YAMADA Tetsuya 東北大学, 医学(系)研究科(研究院), 准教授 (90400374)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 臓器間相互作用 / 褐色脂肪組織 / 肝臓 / 自律神経 / 迷走神経 / 交感神経 |
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| Research Abstract |
Despite remarkable advancements in obesity research over the past decade, the mechanisms underlying obesity are still not fully understood. In this study, we discovered a new inter-organ neural network from the liver. In states of energy intake beyond physiological requirements, glucose metabolism changes in the liver with the induction of neuronal signal transmissions via the vagal nerve. These signals, received by the brain, result in the inactivation of sympathetic innervation of brown adipose tissue (BAT). This leads to suppression of thermogenesis in BAT and thereby favors obesity development. During periods when sufficient food was not always available, this system worked in favor of survival. However, in the current age of plenty, it is assumed to work as a mechanism flipping a metabolic switch toward obesity. Furthermore, the efficacy of the liver-to-BAT interaction differs among mouse strains and these differences may contribute to determining the obesity predispositions.
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[Journal Article] Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization2013
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
Pages: 2316
DOI
Peer Reviewed
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[Journal Article] Cognitive dysfunction associated with anti-glutamic acid decarboxylase autoimmunity : a case-control study2013
Author(s)
Takagi M, Ishigaki Y, Uno K, Sawada S, Imai J, Kaneko K, Hasegawa Y, Yamada T, Tokita A, Iseki K, Kanno S, Nishio Y, Katagiri H, Mori E
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Journal Title
BMC Neurol
Volume: 13
Pages: 295
DOI
Peer Reviewed
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[Journal Article] Chronic mild stress alters circadian expressions of molecular clock genes in the liver2013
Author(s)
Takahashi K, Yamada T (corresponding author), Tsukita S, Kaneko K, Shirai Y, Munakata Y, Ishigaki Y, Imai J, Uno K, Hasegawa Y, Sawada S, Oka Y, Katagiri H
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Journal Title
Am J Physiol Endocrinol Metab
Volume: 304(3)
Pages: E301-9
DOI
Peer Reviewed
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[Journal Article] Importance of endothelial NF-κB signaling in vascular remodeling and aortic aneurysm formation2013
Author(s)
Saito T, Hasegawa Y, Ishigaki Y, Yamada T, Gao J, Imai J, Uno K, Kaneko K, Ogihara T, Shimosawa T, Asano T, Fujita T, Oka Y, Katagiri H
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Journal Title
Cardiovasc Res
Volume: 97(1)
Pages: 106-14
DOI
Peer Reviewed
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[Journal Article] Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals2012
Author(s)
Tsukita S, Yamada T, Uno K, Takahashi1 K, Kaneko K, Ishigaki Y, Imai J, Hasegawa Y, Sawada S, Ishihara H, Oka Y, Katagiri H
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Journal Title
Cell Metab
Volume: 16(6)
Pages: 825-32
DOI
Peer Reviewed
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[Journal Article] Blockade of the NF-κB pathway in the endothelium prevents insulin resistance and prolongs lifespans2012
Author(s)
Hasegawa Y, Saito T, Ogihara T, Ishigaki Y, Yamada T, Imai J, Uno K, Gao J, Kaneko K, Shimosawa T, Asano T, Fujita T, Oka Y, Katagiri H
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Journal Title
Circulation
Volume: 125(9)
Pages: 1122-33
DOI
Peer Reviewed
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[Journal Article] Hepatic peroxisome proliferator-activated receptor-g–fat-specific protein 27 pathway contributes to大嶽obesity-related hypertension via afferent vagal signals2012
Author(s)
Uno K, Yamada T, Ishigaki Y, Imai J,Hasegawa Y,Gao J, Kaneko K, Matsusue K, Yamazaki T,Oka Y, Katagiri H
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Journal Title
Eur Heart J
Volume: 33(10)
Pages: 1279-89
DOI
Peer Reviewed
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[Journal Article] Involvement of endoplasmic stress protein C/EBP homologous protein in arteriosclerosis acceleration with augmented biological stress responses2011
Author(s)
Gao J, Ishigaki Y, Yamada T, Kondo K, Yamaguchi S, Imai J, Uno K, Hasegawa Y, Sawada S, Ishihara H, Oyadomari S, Mori M, Oka Y, Katagiri H
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Journal Title
Circulation
Volume: 124(7)
Pages: 830-839
DOI
Peer Reviewed
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[Journal Article] Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRin skeletal muscle2011
Author(s)
Sugita S, Kamei Y, Akaike F, Suganami T, Kanai S, Hattori M, Manabe Y, Fujii N, Takai-Igarashi T, Tadaishi M, Oka J, Aburatani H, Yamada T, Katagiri H, Kakehi S, Tamura Y, Kubo H, Nishida K, Miura S, Ezaki O, Ogawa Y
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Journal Title
PLoS One
Volume: 6(5)
Pages: e20467
DOI
Peer Reviewed
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