Study on the pathophysiological roles of seipin, a generalized lipodystrophy causative gene product
Project/Area Number |
24390237
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Endocrinology
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Research Institution | Jichi Medical University (2014-2015) Kyoto University (2012-2013) |
Principal Investigator |
Ebihara Ken 自治医科大学, 医学部, 准教授 (70362514)
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Co-Investigator(Kenkyū-buntansha) |
ABE MEGUMI 京都大学, 生命科学研究科, 助教 (20568688)
KUSAKABE TORU 京都大学, 医学研究科, 准教授 (60452356)
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Project Period (FY) |
2012-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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Keywords | セイピン / 脂肪萎縮症 / ラットモデル / 精神発達遅滞 / 精子低形成 / レプチン / ラット / 疾患特異的iPS細胞 |
Outline of Final Research Achievements |
Mutations of BSCL2 cause the most severe form of congenital generalized lipodystrophy (CGL). BSCL2mRNAis highly expressed in the brain and testis in addition to the adipose tissue in human, suggesting physiological roles of seipin in non-adipose tissues. Since we found BSCL2 mRNA expression pattern among organs in rat is similar tohumanwhile it is not highly expressed in mouse brain,we generated a Bscl2/seipin knockout (SKO) rat. SKO rats showed total lack of white adipose tissues, while physiologically functional brown adipose tissuewas preserved. Besides the lipodystrophic phenotypes, SKO rats showed impairment of spatial working memory with brainweight reduction and infertility with azoospermia.We confirmed reduction of brain volume and number of sperm in human patients with BSCL2 mutation. This is the first report demonstrating that seipin is necessary for normal brain development and spermatogenesis in addition to white adipose tissue development.
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Report
(5 results)
Research Products
(55 results)
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[Journal Article] Impaired adipogenic capacity in induced pluripotent stem cells from lipodystrophic patients with BSCL2 mutations2016
Author(s)
1.E. Mori, J. Fujikura, M. Noguchi, K. Nakao, M. Matsubara, M. Sone, D. Taura, T. Kusakabe, K. Ebihara, T. Tanaka, K. Hosoda, K. Takahashi, I. Asaka, N. Inagaki, K. Nakao
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Journal Title
Metablism
Volume: 65
Issue: 4
Pages: 543-556
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] ・Seipin is necessary for normal brain development and spermatogenesis in addition to adipogenesis.2015
Author(s)
Ebihara C, Ebihara K, Aizawa-Abe M, Mashimo T, Tomita T, Zhao M, Gumbilai VM, Kusakabe T, Yamamoto Y, Aotani D, Yamamoto-Kataoka S, Sakai T, Hosoda K, Serikawa T, Nakao K
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Journal Title
Hum Mol Genet
Volume: 24
Issue: 15
Pages: 4238-4249
DOI
Related Report
Peer Reviewed
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[Journal Article] Leptin improves fatty liver independently of insulin sensitization and appetite suppression in hepatocyte-specific Pten-deficient mice with insulin hypersensitivity.2015
Author(s)
Yamamoto-Kataoka S, Ebihara K, Aizawa-Abe M, Nishio M, Kusakabe T, Yamamoto Y, Aotani D, Sakai T, Zhao M, Ebihara C, Gumbilai VM, Hosoda K, Suzuki A, Nakao K
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Journal Title
Horm Metab Res
Volume: 47
Issue: 03
Pages: 168-175
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Leptin restores the insulinotropic effect of exenatide in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet2014
Author(s)
T. Sakai, T. Kusakabe, K. Ebihara, D. Aotani, S. Yamamoto-Kataoka, Z. Mingming, VM. Gumbilai, C. Ebihara, M. Aizawa-Abe, Y. Yamamoto, M. Noguchi, J. Fujikura, K. Hosoda, N. Inagaki, K. Nakao
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Journal Title
Am J Physiol Endocrinol Metab.
Volume: 307
Issue: 8
Pages: 712-719
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Generation of leptin-deficient Lepmkyo/Lepmkyo rats and identification of leptin-responsive genes in the liver.2013
Author(s)
M. Aizawa-Abe, K. Ebihara, C. Ebihara, T. Mashimo, A. Takizawa, T. Tomita, T. Kusakabe, Y. Yamamoto, D. Aotani, S. Yamamoto-Kataoka, T. Sakai, K. Hosoda, T. Serikawa, K. Nakao
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Journal Title
Physiol Genomics.
Volume: 45(17)
Issue: 17
Pages: 786-793
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] In vitro characterization and engraftment of adipocytes derived from human induced pluripotent stem cells and embryonic stem cells.2013
Author(s)
M. Noguchi, K. Hosoda, E. Mori, M. Nakane, K. Nakao, D. Taura, Y. Yamamoto, T. Kusakabe, M. Sone, H. Sakurai, J. Fujikura, K. Ebihara, K. Nakao
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Journal Title
Stem Cells and Development
Volume: 22(21)
Issue: 21
Pages: 2895-2905
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Intracerebroventricular administration of C-type natriuretic peptide suppresses food intake via activation of the melanocortin system in mice.2013
Author(s)
N. Yamada-Goto, G. Katsuura, K. Ebihara, M. Inuzuka, Y. Ochi, Y. Yamashita, T. Kusakabe, A. Yasoda, N. Asahara-Satoh, H. Ariyasu, K. Hosoda, K. Nakao.
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Journal Title
Diabetes
Volume: 62(5)
Issue: 5
Pages: 1500-1504
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Intracerebroventricular administration of C-type natriuretic peptide suppresses food intake via activation of the melanocortin system in mice.2012
Author(s)
N. Yamada-Goto, G. Katsuura, K. Ebihara, M. Inuzuka, Y. Ochi, Y. Yamashita, T. Kusakabe, A. Yasoda, N. Asahara- Satoh, H. Ariyasu, K. Hosoda. K. Nakao
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Journal Title
J Neuroendocrinol
Volume: (掲載決定)
NAID
Related Report
Peer Reviewed
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[Presentation] Seipin is necessary for normal brain development and spermatogenesis in addition to adipogenesis2015
Author(s)
Ebihara C, Ebihara K, Aizawa-Abe M, Mashimo T, Tomita T, Zhao M, Gumbilai V, Kusakabe T, Yamamoto Y, Aotani D, Yamamoto-Kataoka S, Sakai T, Hosoda K, Serikawa T, Nakao K
Organizer
22nd European Congress on Obesity
Place of Presentation
チェコ共和国、プラハ
Year and Date
2015-05-07
Related Report
Int'l Joint Research
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[Presentation] The human lipodystrophy gene product, seipin plays physiological roles in the brain development and spermatogenesis in addition to the adipogenesis Translational Research of Leptin for Lipodystrophy in Japan2014
Author(s)
Chihiro Ebihara, Ken Ebihara, Megumi Aizawa-Abe, Tomoji Mashimo, Tsutomu Tomita, Mingming Zhao, Valentino Gumbilai, Yuji Yamamoto, Sachiko Yamamoto-Kataoka, Kiminori Hosoda, Tadao Serikawa, Kazuwa Nakao
Organizer
Lipodystrophy in 2014: Leptin and Beyond
Place of Presentation
米国、アナーバー
Year and Date
2014-10-17 – 2014-10-18
Related Report
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[Presentation] The human lipodystrophy gene product, seipin plays physiological roles beyond the adipose tissue2013
Author(s)
Ken Ebihara, Megumi Aizawa-Abe, Tshutomu Tomita, Toru Kusakabe, Yuji Yamamoto, Daisuke Aotani, Sachiko Yamamoto-Kataoka, Takeru Sakai, Valentino Milton Gumbilai, Mingming Zhao, Kiminori Hosoda and Kazuwa Nakao.
Organizer
The Endocrine Society’s 95th Annual Meeting & Expo
Place of Presentation
アメリカ、サンフランシスコ
Related Report
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[Presentation] Benefical Effects of Combination Therapy With Lept in and Exenatide in a Mouse Model of Type2 Diabetes With Increased Adiposity2012
Author(s)
Takeru Sakai, Toru Kusakabe, Ken Ebihara, Daisuke Aotani, Sachiko Kataoka, Chihiro Ebihara, Yuj i Yamamoto, Megumi Abe, Junji Fujikura, Kiminori Hosoda, Kazuwa Nakao
Organizer
2nd scientific sessions American Diabetes Associatic
Place of Presentation
Philadelphia(University)
Year and Date
2012-06-10
Related Report
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[Presentation] Leptin Modulates brain activity associated with feeding behavior in patients with Lipodystrophy.2012
Author(s)
D. Aotani, K. Ebihara, N. Sawamoto, T. Kusakabe, M. Aizawa-Abe, S. Kataoka, T. Sakai, C. Ebihara, J. Fujikura, K. Hosoda, H. Fukuyama & K. Nakao.
Organizer
19th European Congress on Obesity
Place of Presentation
Lyon(Frarnce)
Year and Date
2012-05-10
Related Report
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[Presentation] Leptin Modulates brain activity associated with feeding behavior in patients with Lipodystrophy.2012
Author(s)
D. Aotani, K. Ebihara, N. Sawamoto, T. Kusakabe, M. Aizawa-Abe, S. Kataoka, T. Sakai, C. Ebihara, J. Fujikura, K. Hosoda, H. Fukuyama & K. Nakao.
Organizer
15th International & 14th European Congress of Endocrinology
Place of Presentation
Florence(Italy)
Year and Date
2012-05-05
Related Report
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