Mio/dChREBP coordinately increases fat mass by regulating lipid synthesis and feeding behavior in Drosophila.
Mio/dChREBP coordinately increases fat mass by regulating lipid synthesis and feeding behavior in Drosophila.
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DOI：
10.1016/j.bbrc.2012.08.028
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发表时间：
2012-09-14
影响因子：
3.1
通讯作者：
DiAngelo, Justin R.
中科院分区：
文献类型：
--
作者：
Sassu, Eric D.;McDermott, Jacqueline E.;Keys, Brendan J.;Esmaeili, Melody;Keene, Alex C.;Birnbaum, Morris J.;DiAngelo, Justin R.
在营养过剩期间，甘油三酯被合成和储存，以在饥荒期间提供能量。高葡萄糖的存在导致碳水化合物反应元件结合蛋白（ChREBP）的激活，ChREBP是一种诱导许多糖酵解和脂肪生成酶表达的转录因子。ChREBP在主要的代谢组织中表达，虽然我们对ChREBP在肝脏中的功能有基本的了解，但缺乏研究ChREBP在其他组织中功能的体内遗传系统。在这项研究中，我们的特点的作用，果蝇同系物的ChREBP，Mlx相互作用（MIO），在控制脂肪积累的幼虫和成年苍蝇。在Mio突变体中，高糖诱导的脂肪生成酶mRNA表达被钝化，并且使用RNA干扰降低脂肪体中的Mio水平导致瘦表型。当基因bigmax（ChREBP的结合伴侣Mlx的蝇同源物）在幼虫脂肪体中减少时，也观察到瘦的表型。有趣的是，消耗脂肪体中的Mio导致摄食减少，这是在这些动物中观察到的甘油三酯降低的潜在原因。然而，Mio似乎并不是饥饿诱导行为的一般调节剂，因为降低脂肪体Mio水平对进食或饥饿条件下的睡眠没有影响。总之，这些数据暗示了Mio在控制果蝇脂肪积累中的作用，并表明它可能作为脂肪体中的营养传感器，以协调进食行为与营养可用性。
During nutrient excess, triglycerides are synthesized and stored to provide energy during times of famine. The presence of high glucose leads to the activation of carbohydrate response element binding protein (ChREBP), a transcription factor that induces the expression of a number of glycolytic and lipogenic enzymes. ChREBP is expressed in major metabolic tissues and while we have a basic understanding of ChREBP function in liver, in vivo genetic systems to study the function of ChREBP in other tissues are lacking. In this study, we characterized the role of the Drosophila homolog of ChREBP, Mlx interactor (Mio), in controlling fat accumulation in larvae and adult flies. In Mio mutants, high sugar-induced lipogenic enzyme mRNA expression is blunted and lowering Mio levels specifically in the fat body using RNA interference leads to a lean phenotype. A lean phenotype is also observed when the gene bigmax, the fly homolog of ChREBP’s binding partner Mlx, is decreased in the larval fat body. Interestingly, depleting Mio in the fat body results in decreased feeding providing a potential cause of the lowered triglycerides observed in these animals. However, Mio does not seem to function as a general regulator of hunger-induced behaviors as decreasing fat body Mio levels has no effect on sleep under fed or starved conditions. Together, these data implicate a role for Mio in controlling fat accumulation in Drosophila and suggests that it may act as a nutrient sensor in the fat body to coordinate feeding behavior with nutrient availability.
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影响因子：
10.5
作者：
Dauwalder, B;Tsujimoto, S;Mattox, W
通讯作者：
Mattox, W
DOI：
10.1073/pnas.0702726104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Ja, William W.;Carvalho, Gil B.;Benzer, Seymour
通讯作者：
Benzer, Seymour
DOI：
10.1073/pnas.0401516101
发表时间：
2004-05-11
影响因子：
11.1
作者：
Iizuka, K;Bruick, RK;Uyeda, K
通讯作者：
Uyeda, K
DOI：
10.1016/j.cub.2010.05.029
发表时间：
2010-07-13
期刊：
Current biology : CB
影响因子：
--
作者：
Keene AC;Duboué ER;McDonald DM;Dus M;Suh GS;Waddell S;Blau J
通讯作者：
Blau J
影响因子：
3.7
作者：
DiAngelo, Justin R.;Erion, Renske;Sehgal, Amita
通讯作者：
Sehgal, Amita