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疾患生命工学センター 先端研究セミナーのお知らせです。

講演タイトル:
Brain Site Specific Gene Knockdown with Viral-Mediated RNAi Method: Regulation of
Energy Homeostasis by ERa in the VMN.

講師:Dr. Sergey Musatov
Research Scientist&s_comma; Neurologix Inc.&s_comma; New York

日時:2008 年7 月29 日(火) 14:40-15:40

場所:疾患生命工学センター セミナー室
(医学部一号館 2 階 N206)

Estrogen receptor α (ERα) plays a pivotal role in the regulation of food intake and energy
expenditure by estrogens. We exploited RNA interference mediated by adeno-associated viral
vectors to achieve focused silencing of ERα in the ventromedial nucleus of the hypothalamus
(VMN)&s_comma; a key center of energy homeostasis. After suppression of ERα expression in the VMN&s_comma;
female mice and rats developed a phenotype characteristic for metabolic syndrome and marked by
obesity&s_comma; hyperphagia&s_comma; impaired tolerance to glucose&s_comma; and reduced energy expenditure. Although an
increase in food intake preceded weight gain&s_comma; our data suggest that a leading factor of obesity in this
model is likely a decline in energy expenditure with all three major constituents being affected&s_comma;
including voluntary activity&s_comma; basal metabolic rate&s_comma; and diet-induced thermogenesis. Together&s_comma; these
findings indicate that ERα in the ventromedial nucleus of the hypothalamus neurons plays an
essential role in the control of energy balance and the maintenance of normal body weight.

[参考文献]
1) Musatov S.&s_comma; Chen W.&s_comma; Pfaff D.W.&s_comma; Mobbs C.V.&s_comma; Yang X.J.&s_comma; Clegg D.J.&s_comma; Kaplitt M.G.&s_comma; Ogawa
S. (2007) Silencing of estrogen receptor a in the ventromedial nucleus of hypothalamus
leads to metabolic syndrome. Proceedings of the National Academy of Sciences. 104(7)&s_comma;
pp. 2501-2506.
2) Musatov S&s_comma; Chen W.&s_comma; Pfaff D.W.&s_comma; Kaplitt M.G.&s_comma; Ogawa S. (2006) RNAi-mediated silencing
of estrogen receptor {alpha} in the ventromedial nucleus of hypothalamus abolishes
female sexual behaviors. Proceedings of the National Academy of Sciences. 103(27)&s_comma; pp.
10456-60.
3) Musatov&s_comma; S.A.&s_comma; Scully&s_comma; T.A.&s_comma; Dudus&s_comma; L.&s_comma; and Fisher&s_comma; K.J. (2000) Induction of circular episomes during
adeno-associated virus (AAV) replication. Virol. 275(2)&s_comma; pp. 411-432.

URL: http://env-health.m.u-tokyo.ac.jp/080729.pdf

連絡先:疾患生命工学センター 健康環境医工学部門
(助教)掛山正心(kake@m.u-tokyo.ac.jp) 内線21415




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