2013 Fiscal Year Final Research Report
The expression of beta-oxidation adjustment key factor ACC2 elucidation which aimed at the metabolic syndrome new therapy
| Project/Area Number |
23580139
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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 |
Applied biochemistry
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MORIMOTO Kohkichi 慶應義塾大学, 医学部, 助教 (10468506)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 代謝 / メタボリックシンドローム / 胆汁酸 / 脂質代謝 |
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| Research Abstract |
We propose that Acetyl-CoA Carboxylase 2 (ACC2) is an attractive therapeutic target of metabolic syndrome, and we analyzed the mechanisms implied in the regulation of ACC2 gene expression to develop a brand-new therapeutic approach of metabolic syndrome. Prior to this study, we had found that hepatic ACC2 expression was repressed by cholic acid administration in mice. We had also found that murine ACC2 gene had two different transcription initiation sites with two different transcriptional regulatory regions. In this study, we analyzed the transcriptional regulatory regions by cloning. We also investigated the alterations of the expressions of the ACC2 mRNA subtypes under special conditions such as high-fat feeding, fasting, and refeeding. According to our result, the regulatory mechanisms participated in the expression of the 3-side ACC2 mRNA seemed to become an therapeutic target to improve hepatic energy homeostasis.
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Author(s)
Matsuzaki J, Suzuki H, Tsugawa H, Watanabe M, Hossain S, Arai E, Saito Y, Sekine S, Akaike T, Kanai Y, Mukaisho KI, Auwerx J, Hibi T.
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Journal Title
Gastroenterology
Volume: Aug 8(pii:S0016-5085(13)01154-2)
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Author(s)
Kerr TA, Matsumoto Y, Matsumoto H, Xie Y, Hirschberger LL, Stipanuk MH, Anakk S, Moore DD, Watanabe M, Kennedy S, Davidson NO.
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Journal Title
Hepatol Res
Volume: Aug 23
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[Journal Article] Tysnd1 deficiency in mice interferes with the peroxisomal localization of PTS2 enzymes, causing lipid metabolic abnormalities and male infertility2013
Author(s)
Mizuno Y, Ninomiya Y, Nakachi Y, Iseki M, Iwasa H, Akita M, Tsukui T, Shimozawa N, Ito C, Toshimori K, Nishimukai M, Hara H, Maeba R, Okazaki T, Alodaib AN, Al Amoudi M, Jacob M, Alkuraya FS, Horai Y, Watanabe M, Motegi H, Wakana S, Noda T, Kurochkin IV, Mizuno Y, Schönbach C, Okazaki Y.
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Journal Title
PLoS Genet
Volume: 9(2)
Pages: e1003286
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[Journal Article] Bile acid binding resin improves metabolic control through the induction of energy expenditure2012
Author(s)
Watanabe M(Corresponding Author), Morimoto M, Houten S, Kaneko-Iwasaki N, Sugizaki T, Horai Y, Mataki C, Sato H, Murahashi K, Arita E, Schoonjans K, Suzuki T, Itoh H and Auwerx J.
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Journal Title
PLoS ONE
Volume: 7(8)
Pages: e38285
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[Journal Article] Bile acids induce monocyte differentiation toward IL-12 hypo-producing dendritic cells via a TGR5-dependent pathway2012
Author(s)
Ichikawa R, Takayama T, Yoneno K, Kamada N, Kitazume MT, Higuchi H, Matsuoka K, Watanabe M, Itoh H, Kanai T, Hisamatsu T, Hibi T.
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Journal Title
Immunology
Volume: 136
Pages: 153-62
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[Journal Article] Lowering Bile Acid Pool Size with a Synthetic Farnesoid X Receptor (FXR) Agonist Induces Obesity and Diabetes through Reduced Energy Expenditure2011
Author(s)
Watanabe M (Corresponding Author), Horai Y, Houten SM, Morimoto K, Sugizaki T, Arita E, Mataki C, Sato H, Tanigawara Y, Schoonjans K, Itoh H and Auwerx J.
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Journal Title
J Biol Chem
Volume: 286
Pages: 26913-26920
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