The regulation of metabolic processes by the Indy (I′m Not Dead Yet) (SLC13A5/NaCT) gene was revealed through studies in Drosophila melanogaster and Caenorhabditis elegans. Reducing the expression of Indy in these species extended their life span by a mechanism resembling caloric restriction, without reducing food intake. In D. melanogaster, mutating the Indy gene reduced body fat content, insulin-like proteins and reactive oxygen species production. Subsequent studies indicated that Indy encodes a citrate transporter located on the cell plasma membrane. The transporter is highly expressed in the mammalian liver. We generated a mammalian knock out model deleting the mammalian homolog mIndy (SLC13A5). The knock out animals were protected from HFD induced obesity, fatty liver and insulin resistance. Moreover, we have shown that inducible and liver selective knock down of mIndy protects against the development of fatty liver and insulin resistance and that obese humans with type 2 diabetes and non-alcoholic fatty liver disease have increased levels of mIndy. Therefore, the transporter mINDY (NaCT) has been proposed to be an ‘ideal target for the treatment of metabolic disease’. A small molecule inhibitor of the mINDY transporter has been generated, normalizing glucose levels and reducing fatty liver in a model of diet induced obese mice. Taken together, studies from lower organisms, mammals and humans suggest that mINDY (NaCT) is an attractive target for the treatment of metabolic disease.

代谢过程由印地调节（我'米Ñ OT d EAD Ý等）（SLC13A5 / NACT）基因通过在研究显示黑腹果蝇和线虫。减少Indy在这些物种中的表达可通过类似于热量限制的机制延长其寿命，而不会减少食物的摄入。在黑腹果蝇中，对Indy基因进行突变会降低体内脂肪含量，类胰岛素蛋白和活性氧的产生。随后的研究表明，Indy编码位于细胞质膜上的柠檬酸盐转运蛋白。转运蛋白在哺乳动物肝脏中高度表达。我们生成了删除哺乳动物同源mIndy（SLC13A5）的哺乳动物基因敲除模型。敲除动物免受HFD诱导的肥胖，脂肪肝和胰岛素抵抗。此外，我们已经表明，诱导和选择性击倒mIndy可以防止脂肪肝和胰岛素抵抗的发展，并且患有2型糖尿病和非酒精性脂肪肝的肥胖人类的mIndy水平升高。因此，已经提出转运蛋白mINDY（NaCT）是“治疗代谢疾病的理想靶标”。在饮食诱导的肥胖小鼠模型中，已经产生了mINDY转运蛋白的小分子抑制剂，可正常化葡萄糖水平并减少脂肪肝。总之，来自低等生物，哺乳动物和人类的研究表明，mINDY（NaCT）是治疗代谢性疾病的诱人靶标。