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Title: Hepatocyte-specific deletion of Pparα promotes NAFLD in the context of obesity
Authors: Régnier, Marion
Polizzi, Arnaud
Smati, Sarra
Lukowicz, Céline
Fougerat, Anne
Lippi, Yannick
Fouché, Edwin
Lasserre, Frédéric
Naylies, Claire
Bétoulières, Colette
Barquissau, Valentin
Mouisel, Etienne
Bertrand-Michel, Justine
Batut, Aurélie
Saati, Talal Al
Canlet, Cécile
Tremblay-Franco, Marie
Ellero-Simatos, Sandrine
Langin, Dominique
Postic, Catherine
Wahli, Walter
Loiseau, Nicolas
Guillou, Hervé
Montagner, Alexandra
Keywords: Science::Medicine
Issue Date: 2020
Source: Régnier, M., Polizzi, A., Smati, S., Lukowicz, C., Fougerat, A., Lippi, Y., . . . Montagner, A. (2020). Hepatocyte-specific deletion of Pparα promotes NAFLD in the context of obesity. Scientific Reports, 10(1), 6489-. doi:10.1038/s41598-020-63579-3
Journal: Scientific Reports 
Abstract: 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- deficient mice (Pparα-/-) and in mice lacking Pparα only in hepatocytes (Pparαhep-/-). 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.
ISSN: 2045-2322
DOI: 10.1038/s41598-020-63579-3
Rights: © 2020 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per-mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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