Stéatohépatite non alcoolique

Résumé

La stéatohépatite non alcoolique (ou NASH, de son acronyme anglophone en et par raccourci médiatique, maladie du soda) également appelée maladie du foie gras est une surcharge en graisse du foie (stéatose hépatique) sans rapport avec la prise d'alcool. C’est une maladie le plus souvent asymptomatique, mais dont la prévalence est actuellement en augmentation en raison de la double épidémie mondiale de diabète de type 2 et d'obésité. Chez certains patients, la stéatose évolue vers une fibrose, puis une cirrhose, et parfois un cancer du foie (carcinome hépatocellulaire) confirmant l’intérêt de son diagnostic. Elle pourrait expliquer 16 à 32 % des cytolyses hépatiques inexpliquées et pourrait être ainsi la principale cause des cirrhoses dites cryptogéniques. Les médecins estiment qu'en France six millions de personnes seraient touchées par la NASH. Épidémiologie Il s'agit de l'atteinte hépatique la plus fréquente en Occident où elle constitue la première cause de perturbation

Source officielle

https://fr.wikipedia.org/wiki/St%C3%A9atoh%C3%A9patite_non_alcoolique

À propos de ce résultat

Cette page est générée automatiquement et peut contenir des informations qui ne sont pas correctes, complètes, à jour ou pertinentes par rapport à votre recherche. Il en va de même pour toutes les autres pages de ce site. Veillez à vérifier les informations auprès des sources officielles de l'EPFL.

Publications associées (23)

Publications associées

Chargement

Personnes associées (6)

Personnes associées

Chargement

Unités associées (2)

Unités associées

Chargement

Concepts associés (47)

Concepts associés

Chargement

Cours associés (1)

Cours associés

Chargement

Séances de cours associées (1)

Séances de cours associées

Chargement

In Vitro Human Liver Model of Nonalcoholic Steatohepatitis by Coculturing Hepatocytes, Endothelial Cells, and Kupffer Cells

Soufian Lasli

The liver has a complex and unique microenvironment with multiple cell-cell interactions and internal vascular networks. Although nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with multiple phases, no proper model could fully recapitulate the in vivo microenvironment to understand NAFLD progression. Here, an in vitro human liver model of NAFLD by coculturing human hepatocytes, umbilical vein endothelial cells (HUVECs), and Kupffer cells (KCs) into spheroids is presented. Analysis of indirect cross-talk using conditioned media between steatotic spheroids-composed of hepatocellular carcinoma-derived cells (HepG2) and HUVECs-and mouse KCs reveals that the latter can be activated showing increased cell area, elevated production of reactive oxygen species (ROS), and proinflammatory cytokines. Spheroids incorporating human KCs (HKCs) can also be induced into steatotic stage by supplementing fat. Steatotic spheroids with/without HKCs show different levels of steatotic stages through lipid accumulation and ROS production. Steatotic spheroids made from an immortalized hepatic progenitor cell line (HepaRG) compared to those made from HepG2 cells display similar trends of functionality, but elevated levels of proinflammatory cytokines, and improved reversibility of steatosis. The in vitro human liver system proposed makes strides in developing a model to mimic and monitor the progression of NAFLD.

2019

Chargement

The liver possesses a unique microenvironment with a complex internal vascular system and cell-cell interactions. Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease, and although much effort has been dedicated to building models to target NAFLD, most in vitro systems rely on simple models failing to recapitulate complex liver functions. Here, an in vitro system is presented to study NAFLD (steatosis) by coculturing human hepatocellular carcinoma (HepG2) cells and umbilical vein endothelial cells (HUVECs) into spheroids. Analysis of colocalization of HepG2-HUVECs along with the level of steatosis reveals that the NAFLD pathogenesis could be better modeled when 20% of HUVECs are presented in HepG2 spheroids. Spheroids with fat supplements progressed to the steatosis stage on day 2, which could be maintained for more than a week without being harmful for cells. Transferring spheroids onto a chip system with an array of interconnected hexagonal microwells proves helpful for monitoring functionality through increased albumin secretions with HepG2-HUVEC interactions and elevated production of reactive oxygen species for steatotic spheroids. The reversibility of steatosis is demonstrated by simply stopping fat-based diet or by antisteatotic drug administration, the latter showing a faster return of intracellular lipid levels to the basal level.

2019

Chargement

, , , ,

Background & Aims: Mitochondria) dysfunction, oxidative stress, inflammation, and metabolic reprograming are crucial contributors to hepatic injury and subsequent liver fibrosis. Poly(ADP-ribose) polymerases (PARP) and their interactions with sirtuins play an important role in regulating intermediary metabolism in this process. However, there is little research into whether PARP inhibition affects alcoholic and non-alcoholic steatohepatitis (ASH/NASH). Methods: We investigated the effects of genetic deletion of PARP1 and pharmacological inhibition of PARP in models of early alcoholic steatohepatitis, as well as on Kupffer cell activation in vitro using biochemical assays, real-time PCR, and histological analyses. The effects of PARP inhibition were also evaluated in high fat or methionine and choline deficient diet-induced steatohepatitis models in mice. Results: PARP activity was increased in livers due to excessive alcohol intake, which was associated with decreased NAD content and SIRT1 activity. Pharmacological inhibition of PARP restored the hepatic NAD+ content, attenuated the decrease in SIRT1 activation and beneficially affected the metabolic-, inflammatory-, and oxidative stress-related alterations due to alcohol feeding in the liver. PARP1(-/-) animals were protected against alcoholic steatohepatitis and pharmacological inhibition of PARP or genetic deletion of PARP1 also attenuated Kupffer cell activation in vitro. Furthermore, PARP inhibition decreased hepatic triglyceride accumulation, metabolic dysregulation, or inflammation and/or fibrosis in models of NASH. Conclusion: Our results suggests that PARP inhibition is a promising therapeutic strategy in steatohepatitis with high translational potential, considering the availability of PARP inhibitors for clinical treatment of cancer. Lay summary: Poly(ADP-ribose) polymerases (PARP) are the most abundant nuclear enzymes. The PARP inhibitor olaparib (Lynparza) is a recently FDA-approved therapy for cancer. This study shows that PARP is overactivated in livers of subjects with alcoholic liver disease and that pharmacological inhibition of this enzyme with 3 different PARP inhibitors, including olaparib, attenuates high fat or alcohol induced liver injury, abnormal metabolic alteration, fat accumulation, inflammation and/or fibrosis in preclinical models of liver disease. These results suggest that PARP inhibition is a promising therapeutic strategy in the treatment of alcoholic and non-alcoholic liver diseases. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

Elsevier Science Bv2017

Chargement

, , , ,

Elsevier Science Bv2017