Nutritional related liver disease: targeting the endoplasmic reticulum stress

作者：Kammoun Helene L; Hainault Isabelle; Ferre Pascal; Foufelle Fabienne^*

来源：Current Opinion in Clinical Nutrition and Metabolic Care, 2009, 12(6): 575-582.

DOI：10.1097/MCO.0b013e32833189db

• endoplasmic reticulum stress
• hepatic steatosis
• metabolic syndrome
• NAFLD

Purpose of review
Nutritional hepatic disorders are spreading worldwide associated to obesity and type 2 diabetes. The underlying mechanisms leading to the development of hepatic steatosis and its complications are not fully understood. The endoplasmic reticulum (ER) stress response has recently been proposed to play a crucial role in the setting of these pathologies. This review will evaluate the late discoveries highlighting ER stress as a major actor in the development of nutritional liver diseases.
Recant findings
Activation of ER stress has been reported in the fatty liver of obese rodents and obese individuals. The mechanisms by which ER stress leads to the development of hepatic steatosis have been recently documented. ER stress has been shown to directly activate the lipogenic transcription factor SREBP-1c (sterol regulatory element binding protein-1c) conducting to an induction of the lipogenic pathway. ER stress activation is also associated with impaired VLDL (very low density lipoprotein) secretion. ER stress could also have a role in hepatic steatosis progression by triggering inflammation and fibrosis. In rodents, therapies aiming to reduce ER stress have fully demonstrated their efficiency in the treatment of hepatic steatosis.
Summary
ER stress has been recently involved in the development of hepatic steatosis. Thus, ER stress could represent in the future an eligible therapeutic target for the treatment of nonalcoholic fatty liver disease. However, as ER stress is a fundamental mechanism involved in cell survival, any modification of this pathway must be carefully assessed.

• 出版日期2009-11