2012 Fiscal Year Final Research Report
Development and analysis of model rats for diseases of endocrinology and metabolism
| Project/Area Number |
23659476
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Endocrinology
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| Research Institution | Kyoto University |
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Principal Investigator |
NAKAO Kazuwa 京都大学, 医学研究科, 教授 (00172263)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 疾患モデルラット / エネルギー代謝 / 脂肪細胞 / レプチン |
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| Research Abstract |
Using the method with ENU (N-ethyl-N-nitrosourea) mutagenesis, we generated a leptin deficient Lep^(mkyo)/Lep^(mkyo)rat that had a nonsense mutation (Q92X) in leptin gene. Lep^(mkyo)/Lep^(mkyo)rats showed obese phenotypes including fatty liver, which werecomparable to Lepob/Lepobmice. Lep^(mkyo)/Lep^(mkyo) rat is the treatable rat model lacking leptin signal and will bring further understanding of obesity and its complications.Mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2) are the underlying defect in patients with congenital generalized lipodystrophy type 2. Using the method with ENU (N-ethyl-N-nitrosourea) mutagenesis, we generated a seipin deficient (seipin KO) rat that had a premature stop codon (L20X) in BSCL2. The present study clearly revealed the physiological roles of seipin not only in adipose tissue but also brain and testis.
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[Journal Article] Leptin activates hepatic 5' AMP-Activated Protein Kinase through sympathetic nervous system and α1 adrenergic receptor: A potential mechanism for improvement of fatty liver in lipodystrophy by leptin2012
Author(s)
L. Miyamoto, K. Ebihara, T. Kusakabe, D. Aotani, S. Yamamoto-Kataoka, T. Sakai, M. Aizawa-Abe, Y. Yamamoto, J. Fujikura, T. Hayashi, K. Hosoda, K. Nakao
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Journal Title
J Biol Chem
Volume: 287巻
Pages: 40441-40447
DOI
Peer Reviewed
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[Journal Article] Functional Magnetic Resonance Imaging Analysis of Food-Related Brain Activity in Patients with Lipodystrophy Undergoing Leptin Replacement Therapy2012
Author(s)
D. Aotani, K. Ebihara, N. Sawamoto, T. Kusakabe, M. Aizawa-Abe, S. Kataoka, T. Sakai, H. Iogawa, C. Ebihara, J. Fujikura, K. Hosoda, H. Fukuyama, K. Nakao
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Journal Title
J Clin Endocrinol Metab
Volume: 97巻
Pages: 3663-3671
DOI
Peer Reviewed
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[Journal Article] Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice2012
Author(s)
T. Kusakabe, K. Ebihara, T. Sakai, L. Miyamoto, D. Aotani, Y. Yamamoto, S. Yamamoto-Kataoka, M. Aizawa-Abe, J. Fujikura, K. Hosoda, K. Nakao
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Journal Title
Am J Physiol Endocrinol Metab
Volume: 302巻
Pages: E924-931
DOI
Peer Reviewed
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[Journal Article] Therapeutic impact of leptin on diabetes, diabetic complications, and longevity in insulin-deficient diabetic mice2011
Author(s)
M. Naito, J. Fujikura, K. Ebihara, F. Miyanaga, H. Yokoi, T. Kusakabe, Y. Yamamoto, C. Son, M. Mukoyama, K. Hosoda, K. Nakao
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Journal Title
Diabetes
Volume: 9巻
Pages: 2265-2273
DOI
Peer Reviewed
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