title: Ursodeoxycholyl Lysophosphatidylethanolamide modifies aberrant lipid profiles in NAFLD.
abstract: BACKGROUND
  Hepatic fat accumulation with disturbed lipid homoeostasis is a hallmark of nonalcoholic fatty liver disease (NAFLD). The bile acid phospholipid conjugate Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a novel anti-inflammatory agent with hepatoprotective effects in murine high-fat-diet (HFD)-induced NAFLD. The aim of this work was to study changes in the hepatic lipidome due to UDCA-LPE.
  
  
  METHODS
  High fat diet mouse model, mass spectometry, RT-PCR.
  
  
  RESULTS
  Hepatic lipid extracts of HFD mice were analysed by mass spectrometry. The results determined higher levels of total, saturated, mono- and diunsaturated fatty acids (FA) in HFD mice, which were decreased by UDCA-LPE predominantly by the reducing the most abundant FA species palmitic acid and oleic acid. Unlike other FA species, levels of long-chain polyunsaturated fatty acids (LCPUFA), which are composed of arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were increased in HFD mice upon UDCA-LPE treatment, mainly due to elevated hepatic ARA pools. Analysis of hepatic phospholipids species showed a decrease in total phosphatidylcholine (PC), especially monounsaturated PC (PUFA-PC) levels in HFD mice. Loss of total PC was reversed due to UDCA-LPE by increasing hepatic PUFA-PC pools. Gene expression analysis showed that UDCA-LPE upregulated PPARα, a key transcriptional regulator of fatty acid oxidation, as well as downstream target genes CPT1α and AOX, which are crucially involved in mitochondrial and peroxisomal fatty acid oxidation.
  
  
  CONCLUSIONS
  UDCA-LPE modulates defective fatty acid metabolism during experimental NAFLD thereby restoring altered lipid profiles in addition to its pronounced anti-inflammatory effects. Thus, UDCA-LPE may be a promising drug candidate for the management of NAFLD.
authors.affiliation: Department of Internal Medicine IV, Gastroenterology and Hepatology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Pathil
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.affiliation: Department of General Pediatrics, Division of Inborn Metabolic Diseases, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jürgen G
authors.initials: JG
authors.lastname: Okun
authors.affiliation: Department of Internal Medicine IV, Gastroenterology and Hepatology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Walee
authors.initials: W
authors.lastname: Chamulitrat
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.affiliation: Department of Internal Medicine IV, Gastroenterology and Hepatology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
mesh_terms: D042931:Aldehyde Oxidase / Q000187:drug effects / Q000235:genetics; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000187:drug effects / Q000235:genetics; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D013058:Mass Spectrometry; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D047493:PPAR alpha / Q000187:drug effects / Q000235:genetics; D010713:Phosphatidylcholines / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002756:Cholagogues and Choleretics; D005227:Fatty Acids; D008246:Lysophospholipids; D047493:PPAR alpha; D010713:Phosphatidylcholines; D012333:RNA, Messenger; C000598975:ursodeoxycholyl lysophosphatidylethanolamide; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D014580:Ursodeoxycholic Acid; D015118:Eicosapentaenoic Acid; D042931:Aldehyde Oxidase; D002334:Carnitine O-Palmitoyltransferase
keywords: Fatty acid composition; UDCA-LPE; non-alcoholic fatty liver disease