Ursodeoxycholyl Lysophosphatidylethanolamide modifies aberrant lipid profiles in NAFLD

Eur J Clin Invest. 2015 Sep;45(9):925-31. doi: 10.1111/eci.12486. Epub 2015 Jul 14.


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.

Materials and 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.

Conclusion: 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.

Keywords: Fatty acid composition; UDCA-LPE; non-alcoholic fatty liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Oxidase / drug effects
  • Aldehyde Oxidase / genetics
  • Animals
  • Arachidonic Acid / metabolism
  • Carnitine O-Palmitoyltransferase / drug effects
  • Carnitine O-Palmitoyltransferase / genetics
  • Cholagogues and Choleretics / pharmacology*
  • Diet, High-Fat
  • Disease Models, Animal
  • Docosahexaenoic Acids / metabolism
  • Eicosapentaenoic Acid / metabolism
  • Fatty Acids / metabolism
  • Lipid Metabolism / drug effects*
  • Liver / drug effects*
  • Liver / metabolism
  • Lysophospholipids / pharmacology*
  • Mass Spectrometry
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Oxidation-Reduction / drug effects
  • PPAR alpha / drug effects
  • PPAR alpha / genetics
  • Phosphatidylcholines / metabolism
  • RNA, Messenger / drug effects*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Transcriptome / drug effects
  • Ursodeoxycholic Acid / analogs & derivatives*
  • Ursodeoxycholic Acid / pharmacology


  • Cholagogues and Choleretics
  • Fatty Acids
  • Lysophospholipids
  • PPAR alpha
  • Phosphatidylcholines
  • RNA, Messenger
  • ursodeoxycholyl lysophosphatidylethanolamide
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Ursodeoxycholic Acid
  • Eicosapentaenoic Acid
  • Aldehyde Oxidase
  • Carnitine O-Palmitoyltransferase