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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。

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.

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.
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