期刊
CELL REPORTS
卷 37, 期 5, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.109938
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资金
- SDU2020 Initiative
- Novo Nordisk Foundation
- Independent Research Fund Denmark (Sapere Aude Starting Grant)
- Danish National Research Foundation [141]
- Korea Technology & Information Promotion Agency for SMEs (TIPA) [141] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The transition from a fasted to a fed state leads to extensive transcriptional remodeling in hepatocytes, with a subset of hepatic feeding-induced genes requiring glucocorticoid receptor (GR) for full expression. This includes the important gene Gck, which is involved in hepatic glucose metabolism. GR cooperatively regulates hepatic Gck expression with insulin in a direct manner, affecting postprandial glucose uptake and storage in the liver.
The transition from a fasted to a fed state is associated with extensive transcriptional remodeling in hepato-cytes facilitated by hormonal- and nutritional-regulated transcription factors. Here, we use a liver-specific glucocorticoid receptor (GR) knockout (L-GRKO) model to investigate the temporal hepatic expression of GR target genes in response to feeding. Interestingly, in addition to the well-described fasting-regulated genes, we identify a subset of hepatic feeding-induced genes that requires GR for full expression. This includes Gck, which is important for hepatic glucose uptake, utilization, and storage. We show that insulin and glucocorticoids cooperatively regulate hepatic Gck expression in a direct GR-dependent manner by a 4.6 kb upstream GR binding site operating as a Gck enhancer. L-GRKO blunts preprandial and early postprandial Gck expression, which ultimately affects early postprandial hepatic glucose uptake, phosphorylation, and glycogen storage. Thus, GR is positively involved in feeding-induced gene expression and important for postprandial glucose metabolism in the liver.
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