Pathil, Anita and Liebisch, Gerhard and Okun, Juergen G. and Chamulitrat, Walee and Schmitz, Gerd and Stremmel, Wolfgang (2015) Ursodeoxycholyl Lysophosphatidylethanolamide modifies aberrant lipid profiles in NAFLD. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 45 (9). pp. 925-931. ISSN 0014-2972, 1365-2362
Full text not available from this repository. (Request a copy)Abstract
BackgroundHepatic 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 methodsHigh fat diet mouse model, mass spectometry, RT-PCR. ResultsHepatic 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 PPAR, a key transcriptional regulator of fatty acid oxidation, as well as downstream target genes CPT1 and AOX, which are crucially involved in mitochondrial and peroxisomal fatty acid oxidation. ConclusionUDCA-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FATTY LIVER-DISEASE; ACID-COMPOSITION; QUANTIFICATION; INFLAMMATION; STEATOSIS; ISOMERS; Fatty acid composition; non-alcoholic fatty liver disease; UDCA-LPE |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Jun 2019 13:50 |
| Last Modified: | 13 Jun 2019 13:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4942 |
Actions (login required)
 |
View Item |
