title: Endoplasmic reticulum stress: a new actor in the development of hepatic steatosis.
abstract: OBJECTIVE
  To examine the role of endoplasmic reticulum stress in the regulation of hepatic lipid metabolism and its contribution to the development of hepatic steatosis.
  
  
  RESULTS
  Endoplasmic reticulum stress activation has been reported in most models of hepatic steatosis in rodents and humans and its contribution to hepatic fat deposition has been recently documented. The main metabolic pathway affected by endoplasmic reticulum stress is lipogenesis. Endoplasmic reticulum stress activates the proteolytic cleavage of the lipogenic transcription factor sterol regulatory element binding protein-1c leading to the induction of lipogenic enzyme expression. A role for X box-binding protein 1, an endoplasmic reticulum stress-activated transcription factor, has also recently emerged. Endoplasmic reticulum stress, by inhibiting apoB100 secretion, has associated with impaired VLDL secretion. In rodents, treatments with molecular or chemical chaperones that reduce endoplasmic reticulum stress markers have fully demonstrated their efficiency in the treatment of hepatic steatosis.
  
  
  CONCLUSIONS
  Manipulating endoplasmic reticulum stress pathway yields encouraging results for the treatment of hepatic steatosis in rodents. However, activation of unfolded protein response is a physiological mechanism, which is particularly important for secretory cells such as hepatocytes and the long-term consequences of such treatments should be cautiously evaluated.
authors.affiliation: INSERM UMR-S 872, Centre de Recherche des Cordeliers and Université Pierre et Marie Curie-Paris 6, Paris, France.
authors.forename: Mélissa
authors.initials: M
authors.lastname: Flamment
authors.forename: Hélène L
authors.initials: HL
authors.lastname: Kammoun
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hainault
authors.forename: Pascal
authors.initials: P
authors.lastname: Ferré
authors.forename: Fabienne
authors.initials: F
authors.lastname: Foufelle
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018384:Oxidative Stress; D011489:Protein Denaturation