生物谷報道：據(jù)美國的一個權(quán)威機構(gòu)的調(diào)查顯示,，接近三分之一的美國人都是胖子,，另外有三分之一則是體重超標(biāo),。體重的過多增加由能量平衡的改變誘發(fā),。但是,，是什么因子決定了人的飯量還不清楚,。
來自美國Tufts大學(xué)醫(yī)學(xué)院的Maribel Rios博士的研究組首次證實一種叫做腦衍生神經(jīng)營養(yǎng)因子（BDNF, brain-derived neurotrophic factor,生物谷注）是介導(dǎo)成年小鼠饑飽的關(guān)鍵,。他們的發(fā)現(xiàn)公布在12月26日的Journal of Neuroscience雜志上。
兩個大腦食欲調(diào)控區(qū)域中的Bdnf基因被敲除的小鼠,，其食量明顯增加,，并且比對照明顯增重。研究人員表示,，在這項研究前,，他們已經(jīng)知道BDNF或其受體在發(fā)育過程中的完全缺失會導(dǎo)致年輕小鼠食量過大和肥胖。但是,，他們還不清楚是否BDNF是否在成年動物中也介導(dǎo)饑飽,。
他們最新的發(fā)現(xiàn)表明,，BDNF在VMH(ventromedial，丘腦腹內(nèi)側(cè))和dorsomedial hypothalamus（DMH）中的合成是正常能量平衡的必須條件,。另外,，由于研究中使用的小鼠進(jìn)行了基因改造，因此研究人員能夠確定BDNF在成熟大腦中充當(dāng)饑飽信號,，該過程獨立于發(fā)育大腦的功能,。這個重要差異將可能幫助確定疾病機制和肥胖干擾治療的關(guān)鍵時間。
研究人員表示,，BDNF缺失小鼠的肥胖可能是由于過度消費卡路里導(dǎo)致,。當(dāng)食物量被限制時，突變小鼠能夠恢復(fù)到正常體重范圍,。這意味著VMH和DMH中Bdnf基因的敲除不會影響能量的支出,。
此前，在10月29日的《國際生物信息研究和應(yīng)用雜志》上,，來自美國猶他州楊伯翰大學(xué)的研究人員報道說,，他們發(fā)現(xiàn)了基因在人體肥胖癥中起主要作用的新證據(jù)。
新發(fā)現(xiàn)雖然是針對具有異常高肥胖癥比例的現(xiàn)代北美印第安人的遺傳基因的研究,，但研究人員認(rèn)為肥胖遺傳基因有可能同樣存在于其他人群中,。之前的研究顯示，生活在亞利桑那州和新墨西哥州索諾拉雷沙漠的北美印第安人具有較高的新陳代謝率,。楊伯翰大學(xué)研究人員馬克·羅和同事們對此現(xiàn)象進(jìn)行了研究,，并將重點放在研究對象體內(nèi)被稱為單核苷酸多態(tài)性（SNP）的線粒體DNA變異上。
在研究中,，他們先對200名患有肥胖癥的北美印第安人的新陳代謝速度進(jìn)行了測定,，結(jié)果顯示三分之二的患者其單核苷酸多態(tài)性影響了新陳代謝率。然后,，研究人員又利用TreeSAAP遺傳軟件分析了這些SNP引起的生化變化,，并在107種不同的哺乳動物中追蹤了這些基因變異的進(jìn)化選擇過程。
研究組推測,，較高的新陳代謝率可能具有進(jìn)化優(yōu)勢,。單核苷酸多態(tài)性（SNP）在北美印第安人的歷史發(fā)展中幫助他們在苛刻的食物供應(yīng)環(huán)境中生存下來，但在目前的卡路里攝入過高環(huán)境中,，這種較高的新陳代謝率發(fā)揮了不適當(dāng)?shù)淖饔?，可能?dǎo)致他們出現(xiàn)高比例的肥胖者。
生物谷推薦英文原文：
The Journal of Neuroscience, December 26, 2007, 27(52):14265-14274; doi:10.1523/JNEUROSCI.3308-07.2007
Behavioral/Systems/Cognitive
Selective Deletion of Bdnf in the Ventromedial and Dorsomedial Hypothalamus of Adult Mice Results in Hyperphagic Behavior and Obesity
Thaddeus J. Unger,1 German A. Calderon,2 Leila C. Bradley,3 Miguel Sena-Esteves,4 and Maribel Rios2
Departments of 1Physiology and 2Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, 3Wyeth Pharmaceuticals, Cambridge, Massachusetts 02140, and 4Departments of Neurology and Neuroscience, Molecular Neurogenetics Unit, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129
Correspondence should be addressed to Maribel Rios, Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Avenue, Boston, MA 02111. Email: [email protected]
Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are expressed in several hypothalamic and hindbrain nuclei involved in regulating energy homeostasis, developmentally and in the adult animal. Their depletion during the fetal or early postnatal periods when developmental processes are still ongoing elicits hyperphagic behavior and obesity in mice. Whether BDNF is a chief element in appetite control in the mature brain remains controversial. The required sources of this neurotrophin are also unknown. We show that glucose administration rapidly induced BDNF mRNA expression, mediated by Bdnf promoter 1, and TrkB transcription in the ventromedial hypothalamus (VMH) of adult mice, consistent with a role of this pathway in satiety. Using viral-mediated selective knock-down of BDNF in the VMH and dorsomedial hypothalamus (DMH) of adult mice, we were able to elucidate the physiological relevance of BDNF in energy balance regulation. Site-specific mutants exhibited hyperphagic behavior and obesity but normal energy expenditure. Furthermore, intracerebroventricular administration of BDNF triggered an immediate neuronal response in multiple hypothalamic nuclei in wild-type mice, suggesting that its anorexigenic actions involve short-term mechanisms. Locomotor, aggressive, and depressive-like behaviors, all of which are associated with neural circuits involving the VMH, were not altered in VMH/DMH-specific BDNF mutants. These findings demonstrate that BDNF is an integral component of central mechanisms mediating satiety in the adult mouse and, moreover, that its synthesis in the VMH and/or DMH is required for the suppression of appetite.
Key words: BDNF; VMH; DMH; satiety; obesity; adult
