Hepatocyte-specific deletion of Pparα promotes NAFLD in the context of obesity.

Détails

ID Serval
serval:BIB_F9275B48B31C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Hepatocyte-specific deletion of Pparα promotes NAFLD in the context of obesity.
Périodique
Scientific reports
Auteur(s)
Régnier M., Polizzi A., Smati S., Lukowicz C., Fougerat A., Lippi Y., Fouché E., Lasserre F., Naylies C., Bétoulières C., Barquissau V., Mouisel E., Bertrand-Michel J., Batut A., Saati T.A., Canlet C., Tremblay-Franco M., Ellero-Simatos S., Langin D., Postic C., Wahli W., Loiseau N., Guillou H., Montagner A.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
16/04/2020
Peer-reviewed
Oui
Volume
10
Numéro
1
Pages
6489
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Peroxisome proliferator activated receptor α (PPARα) acts as a fatty acid sensor to orchestrate the transcription of genes coding for rate-limiting enzymes required for lipid oxidation in hepatocytes. Mice only lacking Pparα in hepatocytes spontaneously develop steatosis without obesity in aging. Steatosis can develop into non alcoholic steatohepatitis (NASH), which may progress to irreversible damage, such as fibrosis and hepatocarcinoma. While NASH appears as a major public health concern worldwide, it remains an unmet medical need. In the current study, we investigated the role of hepatocyte PPARα in a preclinical model of steatosis. For this, we used High Fat Diet (HFD) feeding as a model of obesity in C57BL/6 J male Wild-Type mice (WT), in whole-body Pparα <sup>-</sup> deficient mice (Pparα <sup>-/-</sup> ) and in mice lacking Pparα only in hepatocytes (Pparα <sup>hep-/-</sup> ). We provide evidence that Pparα deletion in hepatocytes promotes NAFLD and liver inflammation in mice fed a HFD. This enhanced NAFLD susceptibility occurs without development of glucose intolerance. Moreover, our data reveal that non-hepatocytic PPARα activity predominantly contributes to the metabolic response to HFD. Taken together, our data support hepatocyte PPARα as being essential to the prevention of NAFLD and that extra-hepatocyte PPARα activity contributes to whole-body lipid homeostasis.
Pubmed
Open Access
Oui
Création de la notice
25/04/2020 18:58
Dernière modification de la notice
31/07/2020 5:26
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