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Analysis of SCAP N-glycosylation and Trafficking in Human Cells
Published on: November 8, 2016
Carbohydrate responsive element binding protein and lipid homeostasis
Pierre-Damien Denechaud1, Jean Girard, Catherine Postic
1Cochin Institute, Department of Endocrinology, Metabolism and Cancer, Paris Descartes University, CNRS (UMR 8104), Paris, France.
Current Opinion in Lipidology
|May 8, 2008
Summary
Inhibition of carbohydrate-responsive element-binding protein (ChREBP) reduces fat production in the liver and improves metabolic disease in mice. ChREBP is a key target for treating fatty liver and insulin resistance.
Area of Science:
- Metabolic regulation
- Molecular biology
- Hepatology
Background:
- The liver converts excess carbohydrates into fatty acids via de-novo lipogenesis.
- Hepatic steatosis and metabolic diseases arise from excess fatty acids.
- Sterol regulatory element-binding protein 1c and liver X receptor are involved in insulin-mediated lipogenic gene induction.
Purpose of the Study:
- To review the role and regulation of carbohydrate-responsive element-binding protein (ChREBP) in lipid homeostasis.
- To highlight ChREBP as a hepatic glucose sensor regulating lipogenic genes.
- To discuss ChREBP as a potential therapeutic target for metabolic diseases.
Main Methods:
- Review of recent studies on ChREBP regulation and function.
- In vivo studies in obese ob/ob mice demonstrating therapeutic potential.
- Analysis of transcriptional and posttranslational regulation of ChREBP.
Main Results:
- Liver-specific inhibition of ChREBP decreased lipogenesis and improved hepatic steatosis and insulin resistance in mice.
- ChREBP is transcriptionally regulated by glucose and liver X receptor.
- Posttranslational modifications are essential for ChREBP activation.
Conclusions:
- Carbohydrate-responsive element-binding protein (ChREBP) plays a critical role in regulating hepatic lipid metabolism.
- ChREBP is a promising therapeutic target for fatty liver disease and insulin resistance.
- Further understanding of ChREBP regulation is crucial for developing pharmacological treatments.
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