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  • 1
    Online Resource
    Online Resource
    Ex vivo analysis of serum chemerin activity in murine models of obesity
    Elsevier BV ; 2018
    In:  Cytokine Vol. 104 ( 2018-04), p. 42-45
    Details
    In: Cytokine, Elsevier BV, Vol. 104 ( 2018-04), p. 42-45
    Type of Medium: Online Resource
    ISSN: 1043-4666
    URL: Article
    DOI: 10.1016/j.cyto.2018.02.004
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 1463198-2
    SSG: 12
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  • 2
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    Accumulation of cholesterol, triglycerides and ceramides in hepatocellular carcinomas of diethylnitrosamine injected mice
    Springer Science and Business Media LLC ; 2021
    In:  Lipids in Health and Disease Vol. 20, No. 1 ( 2021-12)
    Details
    In: Lipids in Health and Disease, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2021-12)
    Abstract: Dysregulated lipid metabolism is critically involved in the development of hepatocellular carcinoma (HCC). The respective metabolic pathways affected in HCC can be identified using suitable experimental models. Mice injected with diethylnitrosamine (DEN) and fed a normal chow develop HCC. For the analysis of the pathophysiology of HCC in this model a comprehensive lipidomic analysis was performed. Methods Lipids were measured in tumor and non-tumorous tissues by direct flow injection analysis. Proteins with a role in lipid metabolism were analysed by immunoblot. Mann-Whitney U-test or paired Student´s t-test were used for data analysis. Results Intra-tumor lipid deposition is a characteristic of HCCs, and di- and triglycerides accumulated in the tumor tissues of the mice. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha, lipoprotein lipase and hepatic lipase protein were low in the tumors whereas proteins involved in de novo lipogenesis were not changed. Higher rates of de novo lipogenesis cause a shift towards saturated acyl chains, which did not occur in the murine HCC model. Besides, LDL-receptor protein and cholesteryl ester levels were higher in the murine HCC tissues. Ceramides are cytotoxic lipids and are low in human HCCs. Notably, ceramide levels increased in the murine tumors, and the simultaneous decline of sphingomyelins suggests that sphingomyelinases were involved herein. DEN is well described to induce the tumor suppressor protein p53 in the liver, and p53 was additionally upregulated in the tumors. Conclusions Ceramides mediate the anti-cancer effects of different chemotherapeutic drugs and restoration of ceramide levels was effective against HCC. High ceramide levels in the tumors makes the DEN injected mice an unsuitable model to study therapies targeting ceramide metabolism. This model is useful for investigating how tumors evade the cytotoxic effects of ceramides.
    Type of Medium: Online Resource
    ISSN: 1476-511X
    URL: Article
    DOI: 10.1186/s12944-021-01567-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2091381-3
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  • 3
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    Sex-specific changes in triglyceride profiles in liver cirrhosis and hepatitis C virus infection
    Springer Science and Business Media LLC ; 2022
    In:  Lipids in Health and Disease Vol. 21, No. 1 ( 2022-10-24)
    Details
    In: Lipids in Health and Disease, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2022-10-24)
    Abstract: Hepatitis C virus (HCV) infection is associated with serum lipid abnormalities, which partly normalize following direct-acting antiviral (DAA) therapy. Here, associations of serum triglycerides (TGs) with viral genotype and markers of liver disease severity were evaluated in patients with chronic HCV.  Methods The study included the serum of 177 patients with chronic HCV. TGs were quantified by flow injection analysis Fourier transform mass spectrometry. Laboratory values and noninvasive scores for liver fibrosis assessment were determined. The nonparametric Kruskal‒Wallis test, one-way ANOVA, multiple linear regression and Student’s t test were used as appropriate. P values were adjusted for multiple comparisons. Results HCV-infected women had lower serum TGs than men, and thus, a sex-specific analysis was performed. None of the 46 TG species analyzed differed in the serum of female patients with and without liver cirrhosis. In contrast, in the serum of male patients with liver cirrhosis, TGs with 53, 56 and 58 carbon atoms and three to eight double bonds were diminished. These polyunsaturated TGs were also low in males with a high fibrosis-4 score. TGs with 7 or 8 double bonds negatively correlated with the model of end-stage liver disease score in males. In addition, TGs with 49, 51 and 53 carbon atoms were reduced in male patients infected with genotype 3a in comparison to genotype 1a. TGs with 56 carbon atoms were lower in genotype 3a-infected males than in genotype 1b-infected males. TGs did not differ in females by genotype. Genotype 3-related changes disappeared at the end of therapy with DAAs. Overall, the levels of serum TGs did not change during DAA therapy in either sex. Consequently, the serum TGs of males with liver cirrhosis were lower than those of males without cirrhosis at the end of therapy. Such a difference was not apparent in females. Conclusions The decline in TGs observed only in male patients with liver cirrhosis and male patients infected with genotype 3 illustrates sex-specific changes in lipid metabolism in chronic HCV.
    Type of Medium: Online Resource
    ISSN: 1476-511X
    URL: Article
    DOI: 10.1186/s12944-022-01715-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2091381-3
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  • 4
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    Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels are not associated with severity of liver disease and are inversely related to cholesterol in a cohort of thirty eight patients with liver cirrhosis
    Springer Science and Business Media LLC ; 2021
    In:  Lipids in Health and Disease Vol. 20, No. 1 ( 2021-01-18)
    Details
    In: Lipids in Health and Disease, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2021-01-18)
    Abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is of particular importance in cholesterol metabolism with high levels contributing to hypercholesterolemia. Cholesterol and sphingolipids are low in patients with liver cirrhosis. Purpose of this study was to find associations of plasma PCSK9 with circulating cholesterol and sphingolipid species and measures of liver disease severity in patients with liver cirrhosis. Methods PCSK9 protein levels were determined by ELISA in systemic vein (SVP), hepatic vein (HVP) and portal vein plasma of patients with mostly alcoholic liver cirrhosis. PCSK9 and LDL-receptor protein expression were analysed in cirrhotic and non-cirrhotic liver tissues. Results Serum PCSK9 was reduced in patients with liver cirrhosis in comparison to non-cirrhotic patients. In liver cirrhosis, plasma PCSK9 was not correlated with Child-Pugh score, Model for End-Stage Liver Disease score, bilirubin or aminotransferases. A negative association of SVP PCSK9 with albumin existed. PCSK9 protein in the liver did not change with fibrosis stage and was even positively correlated with LDL-receptor protein levels. Ascites volume and variceal size were not related to PCSK9 levels. Along the same line, transjugular intrahepatic shunt to lower portal pressure did not affect PCSK9 concentrations in the three blood compartments. Serum cholesterol, sphingomyelin and ceramide levels did not correlate with PCSK9. Stratifying patients by high versus low PCSK9 levels using the median as cut-off, several cholesteryl ester species were even low in the subgroup with high PCSK9 levels. A few sphingomyelin species were also reduced in the patients with PCSK9 levels above the median. PCSK9 is highly expressed in the liver but systemic, portal and hepatic vein levels were similar. PCSK9 was not correlated with the inflammatory proteins C-reactive protein, IL-6, galectin-3, resistin or pentraxin 3. Of note, HVP PCSK9 was positively associated with HVP chemerin and negatively with HVP adiponectin levels. Conclusions In the cohort of patients with liver cirrhosis mostly secondary to alcohol consumption high PCSK9 was associated with low levels of certain cholesteryl ester and sphingomyelin species. Positive correlations of PCSK9 and LDL-receptor protein in the liver of patients with chronic liver injury are consistent with these findings.
    Type of Medium: Online Resource
    ISSN: 1476-511X
    URL: Article
    DOI: 10.1186/s12944-021-01431-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2091381-3
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  • 5
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    Gender-Specific Differences in Serum Sphingomyelin Species in Patients with Hepatitis C Virus Infection—Sphingomyelin Species Are Related to the Model of End-Stage Liver Disease (MELD) Score in Male Patients
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 9 ( 2023-05-07), p. 8402-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 9 ( 2023-05-07), p. 8402-
    Abstract: Hepatitis C virus (HCV) replication depends on cellular sphingomyelin (SM), but serum SM composition in chronic HCV infection has been hardly analyzed. In this work, 18 SM species could be quantified in the serum of 178 patients with chronic HCV infection before therapy with direct-acting antivirals (DAAs) and 12 weeks later, when therapy was completed. Six SM species were higher in the serum of females than males before therapy and nine at the end of therapy; thus, sex-specific analysis was performed. Type 2 diabetes was associated with lower serum levels of SM 36:2;O2 and 38:2;O2 in men. Serum SM species did not correlate with the viral load in both sexes. Of note, three SM species were lower in males infected with HCV genotype 3 in comparison to genotype 1 infection. These SM species normalized after viral cure. SM 38:1;O2, 40:1;O2, 41:1;O2, and 42:1;O2 (and, thus, total SM levels) were higher in the serum of both sexes at the end of therapy. In males, SM 39:1;O2 was induced in addition, and higher levels of all of these SM species were already detected at 4 weeks after therapy has been started. Serum lipids are related to liver disease severity, and in females 15 serum SM species were low in patients with liver cirrhosis before initiation of and after treatment with DAAs. The serum SM species did not correlate with the model of end-stage liver disease (MELD) score in the cirrhosis and the non-cirrhosis subgroups in females. In HCV-infected male patients, nine SM species were lower in the serum of patients with cirrhosis before DAA treatment and eleven at the end of the study. Most of the SM species showed strong negative correlations with the MELD score in the male cirrhosis patients before DAA treatment and at the end of therapy. Associations of SM species with the MELD score were not detected in the non-cirrhosis male subgroup. In summary, the current analysis identified sex-specific differences in the serum levels of SM species in HCV infection, in liver cirrhosis, and during DAA therapy. Correlations of SM species with the MELD score in male but not in female patients indicate a much closer association between SM metabolism and liver function in male patients.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24098402
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
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  • 6
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    Associations of systemic sphingolipids with measures of hepatic function in liver cirrhosis are related to cholesterol
    Elsevier BV ; 2017
    In:  Prostaglandins & Other Lipid Mediators Vol. 131 ( 2017-07), p. 25-32
    Details
    In: Prostaglandins & Other Lipid Mediators, Elsevier BV, Vol. 131 ( 2017-07), p. 25-32
    Type of Medium: Online Resource
    ISSN: 1098-8823
    URL: Article
    DOI: 10.1016/j.prostaglandins.2017.06.004
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2013367-4
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  • 7
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    Portal vein omentin is increased in patients with liver cirrhosis but is not associated with complications of portal hypertension
    Wiley ; 2013
    In:  European Journal of Clinical Investigation Vol. 43, No. 9 ( 2013-09), p. 926-932
    Details
    In: European Journal of Clinical Investigation, Wiley, Vol. 43, No. 9 ( 2013-09), p. 926-932
    Abstract: Omentin is a visceral fat–derived adipokine associated with endothelium‐dependent vasodilation. Impaired endothelial function is a major cause of portal hypertension in liver cirrhosis. The aim was to assess associations of omentin with systemic markers of endothelial function, namely arginine and asymmetric dimethylarginine ( ADMA ) and complications of portal hypertension in liver cirrhosis. Materials and methods Systemic omentin was measured by ELISA in portal venous serum ( PVS ), systemic venous serum ( SVS ) and hepatic venous serum ( HVS ) of 40 patients with liver cirrhosis and 10 liver‐healthy controls. ADMA and arginine were determined in SVS of the patients by ELISA . Results Omentin is elevated in PVS and tends to be increased in SVS and HVS of patients with liver cirrhosis compared with controls. Omentin is principally expressed in visceral fat, and PVS omentin tends to be higher than SVS levels. Lower HVS than PVS omentin suggests that omentin may be partly removed from the circulation by the liver. Omentin in serum is not associated with stages of liver cirrhosis defined by CHILD ‐ POUGH or MELD score and is not affected in patients with ascites. HVS omentin tends to be reduced in patients with large varices compared with patients without/with small varices. Arginine/ ADMA ratio is reduced in patients with massive ascites but is not associated with variceal size. Further, Arginine/ ADMA ratio does not correlate with omentin. Conclusion Current data show that PVS omentin is increased in liver cirrhosis but is not associated with complications of portal hypertension.
    Type of Medium: Online Resource
    ISSN: 0014-2972 , 1365-2362
    URL: Issue
    URL: Article
    DOI: 10.1111/eci.2013.43.issue-9
    DOI: 10.1111/eci.12122
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 2004971-7
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  • 8
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    The utrophin–beta 2 syntrophin complex regulates adipocyte lipid droplet size independent of adipogenesis
    Springer Science and Business Media LLC ; 2019
    In:  Molecular and Cellular Biochemistry Vol. 452, No. 1-2 ( 2019-2), p. 29-39
    Details
    In: Molecular and Cellular Biochemistry, Springer Science and Business Media LLC, Vol. 452, No. 1-2 ( 2019-2), p. 29-39
    Type of Medium: Online Resource
    ISSN: 0300-8177 , 1573-4919
    URL: Article
    DOI: 10.1007/s11010-018-3409-6
    RVK:
    WD 5725
    RVK:
    WD 5275
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2003615-2
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  • 9
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    Hepatocyte expressed chemerin-156 does not protect from experimental non-alcoholic steatohepatitis
    Springer Science and Business Media LLC ; 2022
    In:  Molecular and Cellular Biochemistry Vol. 477, No. 8 ( 2022-08), p. 2059-2071
    Details
    In: Molecular and Cellular Biochemistry, Springer Science and Business Media LLC, Vol. 477, No. 8 ( 2022-08), p. 2059-2071
    Abstract: Non-alcoholic steatohepatitis (NASH) is a rapidly growing liver disease. The chemoattractant chemerin is abundant in hepatocytes, and hepatocyte expressed prochemerin protected from NASH. Prochemerin is inactive and different active isoforms have been described. Here, the effect of hepatocyte expressed muChem-156, a highly active murine chemerin isoform, was studied in the methionine–choline deficient dietary model of NASH. Mice overexpressing muChem-156 had higher hepatic chemerin protein. Serum chemerin levels and the capability of serum to activate the chemerin receptors was unchanged showing that the liver did not release active chemerin. Notably, activation of the chemerin receptors by hepatic vein blood did not increase in parallel to total chemerin protein in patients with liver cirrhosis. In experimental NASH, muChem-156 had no effect on liver lipids. Accordingly, overexpression of active chemerin in hepatocytes or treatment of hepatocytes with recombinant chemerin did not affect cellular triglyceride and cholesterol levels. Importantly, overexpression of muChem-156 in the murine liver did not change the hepatic expression of inflammatory and profibrotic genes. The downstream targets of chemerin such as p38 kinase were neither activated in the liver of muChem-156 producing mice nor in HepG2, Huh7 and Hepa1-6 cells overexpressing this isoform. Recombinant chemerin had no effect on global gene expression of primary human hepatocytes and hepatic stellate cells within 24 h of incubation. Phosphorylation of p38 kinase was, however, increased upon short-time incubation of HepG2 cells with chemerin. These findings show that muChem-156 overexpression in hepatocytes does not protect from liver steatosis and inflammation.
    Type of Medium: Online Resource
    ISSN: 0300-8177 , 1573-4919
    URL: Article
    DOI: 10.1007/s11010-022-04430-3
    RVK:
    WD 5725
    RVK:
    WD 5275
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2003615-2
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  • 10
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    Lower adiposity does not protect beta-2 syntrophin null mice from hepatic steatosis and inflammation in experimental non-alcoholic steatohepatitis
    Elsevier BV ; 2023
    In:  Gene Vol. 859 ( 2023-04), p. 147209-
    Details
    In: Gene, Elsevier BV, Vol. 859 ( 2023-04), p. 147209-
    Type of Medium: Online Resource
    ISSN: 0378-1119
    URL: Article
    DOI: 10.1016/j.gene.2023.147209
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1491012-3
    SSG: 12
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