Indy mutants: live long and prosper
Indy mutants: live long and prosper
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DOI：
10.3389/fgene.2012.00013
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发表时间：
2012-01-01
影响因子：
3.7
通讯作者：
Rogina, Blanka
中科院分区：
文献类型：
--
作者：
Frankel, Stewart;Rogina, Blanka
Indy编码哺乳动物转运蛋白的蝇同源物，该哺乳动物转运蛋白是克雷布斯循环的二羧酸和三羧酸组分。降低了果蝇Indy或两种C.线虫Indy同系物导致寿命延长。在中间代谢中起关键作用的蝇和虫组织也是Indy基因表达的地方。Indy的小鼠同源物之一（mIndy）主要在肝脏中表达。据推测，INDY活性降低会产生类似于热量限制（CR）的状态。这一假设得到了Indy突变果蝇在高热量食物和对照果蝇在CR上的生理相似性的支持，例如增加的体力活动和体重、产蛋量、甘油三酯水平、耐饥饿性和胰岛素信号传导的降低。此外，Indy突变果蝇经历了在CR动物中也观察到的线粒体生物发生的变化。最近mindy基因敲除小鼠的发现支持并扩展了果蝇的发现。mIndy（-/-）小鼠表现出肝线粒体生物合成、脂质氧化增加和肝脂肪生成减少。当mIndy（-/-）小鼠被喂食高热量食物时，它们被保护免于肥胖和胰岛素抵抗。这些发现表明INDY是治疗代谢综合征、2型糖尿病和肥胖症的潜在药物靶点。
Indy encodes the fly homolog of a mammalian transporter of di and tricarboxylate components of the Krebs cycle. Reduced expression of fly Indy or two of the C. elegans Indy homologs leads to an increase in life span. Fly and worm tissues that play key roles in intermediary metabolism are also the places where Indy genes are expressed. One of the mouse homologs of Indy (mIndy) is mainly expressed in the liver. It has been hypothesized that decreased INDY activity creates a state similar to caloric restriction (CR). This hypothesis is supported by the physiological similarities between Indy mutant flies on high calorie food and control flies on CR, such as increased physical activity and decreases in weight, egg production, triglyceride levels, starvation resistance, and insulin signaling. In addition, Indy mutant flies undergo changes in mitochondrial biogenesis also observed in CR animals. Recent findings with mlndy knockout mice support and extend the findings from flies. mIndy(-/-) mice display an increase in hepatic mitochondrial biogenesis, lipid oxidation, and decreased hepatic lipogenesis. When mIndy(-/-) mice are fed high calorie food they are protected from adiposity and insulin resistance. These findings point to INDY as a potential drug target for the treatment of metabolic syndrome, type 2 diabetes, and obesity.