近日，來自美國德克薩斯大學(xué)西南醫(yī)學(xué)中心的研究人員表示,，他們發(fā)現(xiàn)在下丘腦腹內(nèi)側(cè)核神經(jīng)元內(nèi)轉(zhuǎn)錄因子FOXO1參與調(diào)節(jié)了機(jī)體的能量平衡,。相關(guān)研究成果于6月1日發(fā)表在The Journal of Clinical Investigation上。
之前的研究就已經(jīng)發(fā)現(xiàn),，在包括神經(jīng)細(xì)胞在內(nèi)的許多類型的細(xì)胞中,，轉(zhuǎn)錄因子FOXO1通過調(diào)節(jié)瘦素及胰島素的活性，對(duì)代謝的平衡具有至關(guān)重要的作用,。然而,，介導(dǎo)了FOXO1的調(diào)節(jié)作用的神經(jīng)元及分子靶點(diǎn)目前還不明確。
在這項(xiàng)研究里,，研究人員Joel K. Elmquist表示,，下丘腦的腹內(nèi)側(cè)核(VMH)是FOXO1作用的一個(gè)關(guān)鍵位點(diǎn),。他們發(fā)現(xiàn)，VMH缺失了FOXO1的小鼠表現(xiàn)消瘦,，這歸因于能量消耗增加所致,。而且，在禁食期間,，這種小鼠不能夠適當(dāng)?shù)匾种颇芰康倪^度消耗,。此外，由于骨骼肌以及心肌胰島素敏感性的增加,，這些小鼠的葡萄糖耐受性表現(xiàn)升高,。而進(jìn)一步的基因表達(dá)譜及測序分析表明，有幾種通路被FOXO1所調(diào)節(jié),。除此以外,，他們還發(fā)現(xiàn)，在下丘腦的腹內(nèi)側(cè)核,，核受體SF-1是FOXO1的直接轉(zhuǎn)錄靶點(diǎn),。
該研究表明，在下丘腦的腹內(nèi)側(cè)核神經(jīng)元,，由FOXO1所調(diào)節(jié)的轉(zhuǎn)錄網(wǎng)絡(luò)是調(diào)節(jié)能量平衡以及血糖穩(wěn)態(tài)的關(guān)鍵環(huán)節(jié),。（生物谷Deepblue編譯）
doi: 10.1172/JCI62848
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PMID:
FOXO1 in the ventromedial hypothalamus regulates energy balance
Ki Woo Kim, Jose Donato Jr., Eric D. Berglund, Yun-Hee Choi, Daisuke Kohno, Carol F. Elias, Ronald A. DePinho, Joel K. Elmquist.
The transcription factor FOXO1 plays a central role in metabolic homeostasis by regulating leptin and insulin activity in many cell types, including neurons. However, the neurons mediating these effects and the identity of the molecular targets through which FOXO1 regulates metabolism remain to be defined.Here, we show that the ventral medial nucleus of the hypothalamus (VMH) is a key site of FOXO1 action. We found that mice lacking FOXO1 in steroidogenic factor 1 (SF-1) neurons of the VMH are lean due to increased energy expenditure. The mice also failed to appropriately suppress energy expenditure in response to fasting.Furthermore, these mice displayed improved glucose tolerance due to increased insulin sensitivity in skeletal muscle and heart. Gene expression profiling and sequence analysis revealed several pathways regulated by FOXO1.In addition, we identified the nuclear receptor SF-1 as a direct FOXO1 transcriptional target in the VMH. Collectively, our data suggest that the transcriptional networks modulated by FOXO1 in VMH neurons are key components in the regulation of energy balance and glucose homeostasis.
