Hippo pathway cooperates with ChREBP to regulate hepatic glucose utilization

Hippo pathway plays a crucial role as a regulator of organ size and tumorigenesis that negatively regulates cell growth and survival. Recently lots of evidences show that Hippo pathway plays a crucial role in glucose metabolic metabolism to regulate energy status with cell growth. However, the detai...

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Published in:Biochemical and biophysical research communications 2020-09, Vol.530 (1), p.115-121
Main Authors: Shu, Zhi-ping, Yi, Gui-wen, Deng, Shan, Huang, Kai, Wang, Yan
Format: Article
Language:English
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Summary:Hippo pathway plays a crucial role as a regulator of organ size and tumorigenesis that negatively regulates cell growth and survival. Recently lots of evidences show that Hippo pathway plays a crucial role in glucose metabolic metabolism to regulate energy status with cell growth. However, the detailed mechanism is still unclear. Here we report that Yes-associated protein (YAP), the terminal effector of Hippo pathway, interacts with carbohydrate response element binding protein (ChREBP) in the nucleus of the hepatocytes thereby promoting glycolysis and lipogenesis. A high carbohydrate (HCHO) diet could inactivate the Hippo pathway and encourage the combination of YAP and ChREBP, leading to glucose-induced hepatocyte glycolysis and lipogenesis through up-regulation of target genes such as L-PK and ACC in mice. Conversely, inhibition of YAP activity by phosphorylation or downregulation antagonized glycolysis and lipogenesis in mice fed with HCHO diet. These results suggest that YAP is a nuclear co-factor of ChREBP and that the Hippo pathway negatively affects hepatocyte glycolysis by inhibiting the function of YAP-ChREBP. •YAP binds to the ChREBP in the nucleus of the hepatocytes and promotes its transcriptional activity.•Hippo pathway inhibited ChREBP transcriptional activity through YAP phosphorylation.•Hippo pathway activation inhibited glucose utilization in vivo.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2020.06.105