生物谷報(bào)道：美國(guó)科學(xué)家近日發(fā)現(xiàn)一種基因,，可能為理解為什么肥胖率會(huì)隨年齡增長(zhǎng)而增加提供線索。相關(guān)論文發(fā)表在6月10日的《國(guó)家科學(xué)院院刊》（PNAS）上,。
領(lǐng)導(dǎo)此次研究的是美國(guó)明尼蘇達(dá)大學(xué)醫(yī)學(xué)院的Kevin Wickman,。他和同事在進(jìn)行大腦控制心臟功能的研究時(shí)無(wú)意中發(fā)現(xiàn)，移除小鼠體內(nèi)的某個(gè)特定基因后,，它們易患成年型肥胖（adult-onset obesity）,。
這一基因名為Girk4，研究人員發(fā)現(xiàn)它在視丘下部（hypothalamus）具有特別高的表達(dá)水平,，而視丘下部與調(diào)節(jié)進(jìn)食和能量消耗有關(guān),。Wickman推測(cè)，視丘下部中該基因的正常功能被破壞,，可能是變異小鼠肥胖的潛在原因,。不過(guò)他表示，還需要進(jìn)行更多的研究以弄清其中的具體機(jī)制,。
研究人員表示,，小鼠模型中觀察到的年齡依賴(lài)性肥胖與人類(lèi)肥胖模式很相似。在人類(lèi)中,，20歲到60歲之間肥胖的可能性增加了1倍多,。
論文合著者、明尼蘇達(dá)大學(xué)食品科學(xué)與營(yíng)養(yǎng)學(xué)系的Catherine Kotz說(shuō)：“這是一個(gè)新穎的發(fā)現(xiàn),，可能為理解影響肥胖的潛在細(xì)胞機(jī)制提供重要的新見(jiàn)解,。”（生物谷www.bioon.com）
生物谷推薦原始出處：
PNAS，doi：10.1073/pnas.0803261105,，Cydne A. Perry,，Kevin Wickman
Predisposition to late-onset obesity in GIRK4 knockout mice
Cydne A. Perry*, Marco Pravetoni*, Jennifer A. Teske, Carolina Aguado, Darin J. Erickson, Juan F. Medrano¶, Rafael Luján, Catherine M. Kotz, and Kevin Wickman*,||
*Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455; Minnesota Obesity Center, Department of Food Science and Nutrition, Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, 11G, One Veterans Drive, Minneapolis, MN 55417; Departmento de Ciencias Médicas, Campus Biosanitario C/Almansa, Universidad de Castilla–La Mancha, 14, 02006 Albacete, Spain; Division of Epidemiology, School of Public Health, University of Minnesota, 1300 South Second Street, Suite 300, Minneapolis, MN 54454; and ¶Department of Animal Science, University of California, 1 Shields Avenue, Davis, CA 95616
Communicated by David E. Clapham, Harvard Medical School, Boston, MA, April 7, 2008 (received for review March 5, 2008)
G protein-gated inwardly rectifying potassium (GIRK/Kir3) channels mediate the inhibitory effects of many neurotransmitters on excitable cells. Four Girk genes have been identified (Girk1–4). Whereas GIRK4 is associated with the cardiac GIRK channel, Girk4 expression has been detected in a few neuron populations. Here, we used a transgenic mouse expressing enhanced green fluorescent protein (EGFP) under the control of the Girk4 gene promoter to clarify the expression pattern of Girk4 in the brain. Although small subsets of EGFP-positive neurons were evident in some areas, prominent labeling was seen in the hypothalamus. EGFP expression was most pronounced in the ventromedial, paraventricular, and arcuate nuclei, neuron populations implicated in energy homeostasis. Consistent with a contribution of GIRK4-containing channels to energy balance, Girk4 knockout (–/–) mice were predisposed to late-onset obesity. By 9 months, Girk4–/– mice were 25% heavier than wild-type controls, a difference attributed to greater body fat. Before the development of overweight, Girk4–/– mice exhibited a tendency toward greater food intake and an increased propensity to work for food in an operant task. Girk4–/– mice also exhibited reduced net energy expenditure, despite displaying elevated resting heart rates and core body temperatures. These data implicate GIRK4-containing channels in signaling crucial to energy homeostasis and body weight.
