Pathophysiology of NASH: perspectives for a targeted treatment.

Abstract : Non alcoholic steatohepatitis (NASH) is the more severe form of nonalcoholic fatty liver disease. In NASH, fatty liver, hepatic inflammation, hepatocyte injury and fibrogenesis are associated, and this condition may eventually lead to cirrhosis. Current treatment of NASH relies on the reduction of body weight and increase in physical activity, but there is no pharmacologic treatment approved as yet. Emerging data indicate that NASH progression results from parallel events originating from the liver as well as from the adipose tissue, the gut and the gastrointestinal tract. Thus, dysfunction of the adipose tissue through enhanced flow of free fatty acids and release of adipocytokines, and alterations in the gut microbiome generate proinflammatory signals that underlie NASH progression. Additional 'extrahepatic hits' include dietary factors and gastrointestinal hormones. Within the liver, hepatocyte apoptosis, ER stress and oxidative stress are key contributors to hepatocellular injury. In addition, lipotoxic mediators and danger signals activate Kupffer cells which initiate and perpetuate the inflammatory response by releasing inflammatory mediators that contribute to inflammatory cell recruitment and development of fibrosis. Inflammatory and fibrogenic mediators include chemokines, the cannabinoid system, the inflammasome and activation of pattern-recognition receptors. Here we review the major mechanisms leading to appearance and progression of NASH, focusing on both extrahepatic signals and local inflammatory mechanisms, in an effort to identify the most promising molecular targets for the treatment of this condition.
Type de document :
Article dans une revue
Current Pharmaceutical Design, Bentham Science Publishers, 2013, 19 (29), pp.5250-69
Liste complète des métadonnées

Littérature citée [246 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00801356
Contributeur : Sophie Lotersztajn <>
Soumis le : samedi 15 mars 2014 - 07:00:39
Dernière modification le : mercredi 13 décembre 2017 - 14:44:03
Document(s) archivé(s) le : dimanche 2 avril 2017 - 13:48:17

Fichiers

inserm-00801356_edited.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

  • HAL Id : inserm-00801356, version 1
  • PUBMED : 23394092

Collections

Citation

Fabio Marra, Sophie Lotersztajn. Pathophysiology of NASH: perspectives for a targeted treatment.. Current Pharmaceutical Design, Bentham Science Publishers, 2013, 19 (29), pp.5250-69. 〈inserm-00801356〉

Partager

Métriques

Consultations de la notice

369

Téléchargements de fichiers

940