Role of small leucine zipper protein in hepatic gluconeogenesis and metabolic disorder

查看全文 作　　者：Minsoo [1]Kang;Sun Kyoung [1]Han;Suhyun [1]Kim;Sungyeon [1]Park;Yerin [1]Jo;Hyeryung [1]Kang;Jesang [1]Ko 机构地区：[1]Division of Life Sciences,Korea University,Seoul 02841,South Korea 出　　处：《Journal of Molecular Cell Biology》索引2021年第13卷第5期,共13页 基　　金：This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT and Future Planning(NRF-2017R1E1A1A01073955)and the Korea University Grant. 摘　　要：Hepatic gluconeogenesis is the central pathway for glucose generation in the body.The imbalance between glucose synthesis and uptake leads to metabolic diseases such as obesity,diabetes,and cardiovascular diseases.Small leucine zipper protein(sLZIP)is an isoform of LZIP and it mainly functions as a transcription factor.Although sLZIP is known to regulate the transcription of genes involved in various cellular processes,the role of sLZIP in hepatic glucose metabolism is not known.In this study,we investigated the regulatory role of sLZIP in hepatic gluconeogenesis and its involvement in metabolic disorder.We found that sLZIP expression was elevated during glucose starvation,leading to the promotion of phosphoenolpyruvate carboxylase and glucose-6-phosphatase expression in hepatocytes.However,sLZIP knockdown suppressed the expression of the gluconeogenic enzymes under low glucose conditions.sLZIP also enhanced glucose production in the human liver cells and mouse primary hepatic cells.Fasting-induced cyclic adenosine monophosphate impeded sLZIP degradation.Results of glucose and pyruvate tolerance tests showed that sLZIP transgenic mice exhibited abnormal blood glucose metabolism.These findings suggest that sLZIP is a novel regulator of gluconeogenic enzyme expression and plays a role in blood glucose homeostasis during starvation. 关 键 词：gluconeogenic enzymes hepatic gluconeogenesis HYPERGLYCEMIA transcription factor