Abstract
Citrate is a crucial energy sensor that plays a central role in cellular metabolic homeostasis. The solute carrier family 13 member 5 (SLC13A5), a sodium-coupled citrate transporter highly expressed in the mammalian liver with relatively low levels in the testis and brain, imports citrate from extracellular spaces into the cells. The perturbation of SLC13A5 expression and/or activity is associated with non-alcoholic fatty liver disease, obesity, insulin resistance, cell proliferation, and early infantile epileptic encephalopathy. SLC13A5 has been proposed as a promising therapeutic target for the treatment of these metabolic disorders. In the liver, the inductive expression of SLC13A5 has been linked to several xenobiotic receptors such as the pregnane X receptor and the aryl hydrocarbon receptor as well as certain hormonal and nutritional stimuli. Nevertheless, in comparison to the heightened interest in understanding the biological function and clinical relevance of SLC13A5, studies focusing on the regulatory mechanisms of SLC13A5 expression are relatively limited. In this review, we discuss the current advances in our understanding of the molecular mechanisms by which the expression of SLC13A5 is regulated. We expect this review will provide greater insights into the regulation of the SLC13A5 gene transcription and the signaling pathways involved therein.