Hepatic NAPE-PLD Is a Key Regulator of Liver Lipid Metabolism

Cells

GiulioG. Muccioli¹  Martin Roumain¹  Rita Manco²  Isabelle Leclercq²  Matthias Van Hul³  Marialetizia Rastelli³  PatriceD. Cani³  Charlotte Lefort³  NathalieM. Delzenne³  VincenzoDi Marzo⁴  Nicolas Flamand⁴  Cristoforo Silvestri⁴  Serge Luquet⁵ 

[1] Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, UCLouvain, Université Catholique de Louvain, 1200 Bruxelles, Belgium;Laboratory of Hepato-Gastroenterology, UCLouvain, Université Catholique de Louvain, 1200 Bruxelles, Belgium;Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Bruxelles, Belgium;Quebec Heart and Lung Institute Research Centre, Université Laval, Quebec City, QC G1V 0A6, Canada;Université de Paris, BFA, UMR 8251, CNRS, F-75014 Paris, France;

关键词: NAPE-PLD;    NAEs;    bioactive lipids;    bile acids;    inflammation;    liver;   

DOI  :  10.3390/cells9051247

来源: DOAJ

【 摘 要 】

Diverse metabolic disorders have been associated with an alteration of N-acylethanolamine (NAE) levels. These bioactive lipids are synthesized mainly by N-acylphosphatidylethanolamine-selective phospholipase D (NAPE-PLD) and influence host metabolism. We have previously discovered that NAPE-PLD in the intestine and adipose tissue is connected to the pathophysiology of obesity. However, the physiological function of NAPE-PLD in the liver remains to be deciphered. To study the role of liver NAPE-PLD on metabolism, we generated a new mouse model of inducible Napepld hepatocyte-specific deletion (Napepld^∆Hep mice). In this study, we report that Napepld^∆Hep mice develop a high-fat diet-like phenotype, characterized by an increased fat mass gain, hepatic steatosis and we show that Napepld^∆Hep mice are more sensitive to liver inflammation. We also demonstrate that the role of liver NAPE-PLD goes beyond the mere synthesis of NAEs, since the deletion of NAPE-PLD is associated with a marked modification of various bioactive lipids involved in host homeostasis such as oxysterols and bile acids. Collectively these data suggest that NAPE-PLD in hepatocytes is a key regulator of liver bioactive lipid synthesis and a dysregulation of this enzyme leads to metabolic complications. Therefore, deepening our understanding of the regulation of NAPE-PLD could be crucial to tackle obesity and related comorbidities.

【 授权许可】

Unknown