Ursodeoxycholyl lysophosphatidylethanolamide modifies aberrant lipid profiles in NAFLD

• Verfasst von: Pathil-Warth, Anita [VerfasserIn]
• Verfasst von: Liebisch, Gerhard [VerfasserIn]
• Verfasst von: Okun, Jürgen G. [VerfasserIn]
• Verfasst von: Chamulitrat, Walee [VerfasserIn]
• Verfasst von: Schmitz, Gerd [VerfasserIn]
• Verfasst von: Stremmel, Wolfgang [VerfasserIn]
• Titel: Ursodeoxycholyl lysophosphatidylethanolamide modifies aberrant lipid profiles in NAFLD
• Verf.angabe: Anita Pathil, Gerhard Liebisch, Jürgen G. Okun, Walee Chamulitrat, Gerd Schmitz and Wolfgang Stremmel
• E-Jahr: 2015
• Jahr: 24 June 2015
• Umfang: 7 S.
• Fussnoten: Gesehen am 01.07.2020
• Titel Quelle: Enthalten in: European journal of clinical investigation
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1970
• Jahr Quelle: 2015
• Band/Heft Quelle: 45(2015), 9, Seite 925-931
• ISSN Quelle: 1365-2362
• DOI: doi:10.1111/eci.12486
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Fatty acid composition
• Sach-SW: non-alcoholic fatty liver disease
• Sach-SW: UDCA-LPE
• K10plus-PPN: 1703013441

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. 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.