부산대학교 도서관

High protein diet (HPD) is an affordable and positive approach in prevention and treatment of many diseases. It is believed that transcriptional regulation is responsible for adaptation after HPD feeding and Kruppel-like factor 15 (KLF15), a zinc finger transcription factor that has been proved to perform transcriptional regulation over amino acid, lipid and glucose metabolism, is known to be involved at least in part in this HPD response. To gain more insight into molecular mechanisms by which HPD controls expressions of genes involved in amino acid metabolism in the liver, we performed RNA-seq analysis of mice fed HPD for a short period (3 days). Compared to a low protein diet, HPD feeding significantly increased hepatic expressions of enzymes involved in the breakdown of all the 20 amino acids. Moreover, using KLF15 knockout mice and in vivo Ad-luc analytical system, we were able to identify Cth (cystathionine gamma-lyase) as a new target gene of KLF15 transcription as well as Ast (aspartate aminotransferase) as an example of KLF15-independent gene despite its remarkable responsiveness to HPD. These findings provide us with a clue to elucidate the entire transcriptional regulatory mechanisms of amino acid metabolic pathways. • HPD-fed mouse liver exhibited significant increases in expression of genes involved in the breakdown of all 20 amino acids. • In vivo Ad-luc analysis showed that HPD responses are transcriptionally regulated in the liver. • KLF15 knockout mice helped distinguish HPD responsive genes into KLF15-dependent and -independent pathway groups. • HPD increases Cth expression via KLF15 whereas it elevates Ast in a KLF15-independent manner. [ABSTRACT FROM AUTHOR]