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  • 1
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    Online Resource
    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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  • 2
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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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  • 3
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    Lipopolysaccharide regulated protein expression is only partly impaired in monocytes from patients with type I diabetes
    Springer Science and Business Media LLC ; 2006
    In:  Cardiovascular Diabetology Vol. 5, No. 1 ( 2006-12)
    Details
    In: Cardiovascular Diabetology, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2006-12)
    Abstract: Monocytes play an important role in innate immunity and atherosclerosis. A disturbed secretion of cytokines in lipopolysaccharide (LPS) activated monocytes from type 1 diabetes (T1D) patients has been described and may contribute to the impaired inflammatory response in these individuals. In the present study the influence of LPS on five different proteins with a function in immunity and atherosclerosis was analyzed in monocytes from controls and T1D patients. Methods Monocytes were isolated from controls and T1D patients and the LPS-stimulated increase of IL-6, CXCL8, monocyte chemotactic protein 1 (CCL2, MCP-1) and superoxide dismutase (SOD 2), as well as the LPS-mediated decrease of apolipoprotein E (Apo E) in primary human monocytes from controls and T1D patients was determined. Results CCL2 and IL-6 secretion in response to LPS was found significantly reduced in monocytes from T1D patients when compared to controls whereas basal CCL2 release was similar in control and T1D cells. In contrast, CXCL8 and apolipoprotein E secretion and SOD 2 expression upon LPS stimulation is similar from T1D and control monocytes. Conclusion These data indicate that LPS-mediated protein expression is only partly disturbed in monocytes from T1D patients. Reduced secretion of IL-6 and CCL2 in activated monocytes of these patients may contribute to an impaired inflammatory response and vascular disease.
    Type of Medium: Online Resource
    ISSN: 1475-2840
    URL: Article
    DOI: 10.1186/1475-2840-5-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2006
    detail.hit.zdb_id: 2093769-6
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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)
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    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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    Adiponectin-induced secretion of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1, CCL2) and interleukin-8 (IL-8, CXCL8) is impaired in monocytes from patients with type I diabetes
    Springer Science and Business Media LLC ; 2006
    In:  Cardiovascular Diabetology Vol. 5, No. 1 ( 2006-12)
    Details
    In: Cardiovascular Diabetology, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2006-12)
    Abstract: Systemic adiponectin is reduced in patients with cardiovascular disease (CVD) and low adiponectin may contribute to the pathogenesis of atherosclerosis. However, circulating adiponectin is elevated in type 1 diabetes (T1D) patients, who have also a higher incidence to develop CVD. Because monocytes play an important role in atherosclerosis, we analysed the influence of adiponectin on cytokine and chemokine release in monocytes from T1D patients and controls. Methods Systemic adiponectin was determined in the plasma and the high-molecular weight (HMW) form of adiponectin was analysed by immunoblot. Monocytes were isolated from T1D patients and controls and the adiponectin-stimulated release of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1, CCL2) and interleukin-8 (IL-8, CXCL8) was analysed. Results Systemic adiponectin was higher in T1D patients. Immunoblot analysis of the plasma indicate abundance of HMW adiponectin in T1D patients and controls. IL-6, CCL2 and CXCL8 secretion in response to adiponectin were found induced in monocytes from controls whereas only IL-6 was upregulated in T1D cells. The induction of IL-6 by adiponectin was abrogated by an inhibitor of the NFκB pathway. Conclusion These data indicate that adiponectin-mediated induction of IL-6, CCL2 and CXCL8 is disturbed in monocytes from T1D patients and therefore elevated systemic adiponectin in T1D patients may be less protective when compared to controls.
    Type of Medium: Online Resource
    ISSN: 1475-2840
    URL: Article
    DOI: 10.1186/1475-2840-5-17
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2006
    detail.hit.zdb_id: 2093769-6
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  • 6
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    Altered fecal bile acid composition in active ulcerative colitis
    Springer Science and Business Media LLC ; 2023
    In:  Lipids in Health and Disease Vol. 22, No. 1 ( 2023-11-18)
    Details
    In: Lipids in Health and Disease, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2023-11-18)
    Abstract: Disturbed bile acid homeostasis associated with a rise of primary and a decline of secondary bile acids is a consistent finding in inflammatory bowel diseases (IBDs). Whether fecal bile acids may emerge as biomarkers for IBD diagnosis and disease severity is less clear. Our study aimed to identify associations of 18 fecal bile acid species with IBD entity and disease activity. Methods Stool samples of 62 IBD patients and 17 controls were collected. Eighteen fecal bile acid species were quantified by LC–MS/MS using stable isotope dilution. Lipid levels normalized to a dry weight of the fecal homogenates and ratios of single bile acid species to total bile acid levels were used for calculations. Results IBD patients exhibited altered primary and secondary bile acid ratios in stool, with notable distinctions between ulcerative colitis (UC) compared to Crohn’s disease (CD) and healthy controls. Fecal calprotectin was negatively correlated with glycolithocholic acid (GLCA) and hyodeoxycholic acid (HDCA) in UC. These bile acids were reduced in stool of UC patients with fecal calprotectin levels 〉 500 µg/g compared to UC patients with low calprotectin levels. Moreover, negative associations of six secondary bile acids with C-reactive protein (CRP) existed in UC. In CD patients, fecal bile acids did not correlate with CRP or fecal calprotectin. Diarrhoea is common in IBD, and UC patients with diarrhoea had reduced deoxycholic acid (DCA), glycine conjugated DCA (GDCA) and lithocholic acid in stool in contrast to patients with normal stool consistency. Fecal bile acid levels were not associated with diarrhoea in CD patients. UC patients treated with mesalazine had increased levels of fecal GDCA whereas no such changes were observed in CD patients. Bile acid levels of CD and UC patients treated with biologicals or corticosteroids did not change. Relative levels of GHDCA (specificity: 79%, sensitivity: 67%) and glycochenodeoxycholic acid (specificity: 74%, sensitivity: 63%) were the most specific to distinguish UC from CD. Conclusion Disrupted fecal bile acid homeostasis is associated with disease severity and disease symptoms in UC but not in CD, potentially aiding in distinguishing IBD subtypes and classifying the pathophysiology of diarrhoea in UC.
    Type of Medium: Online Resource
    ISSN: 1476-511X
    URL: Article
    DOI: 10.1186/s12944-023-01971-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2091381-3
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  • 7
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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
    SSG: 12
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  • 8
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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
    SSG: 12
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  • 9
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    The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease
    Springer Science and Business Media LLC ; 1999
    In:  Nature Genetics Vol. 22, No. 4 ( 1999-8), p. 347-351
    Details
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 22, No. 4 ( 1999-8), p. 347-351
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    URL: Article
    DOI: 10.1038/11914
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1999
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 10
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    The role of 'adipotropins' and the clinical importance of a potential hypothalamic–pituitary–adipose axis
    Springer Science and Business Media LLC ; 2006
    In:  Nature Clinical Practice Endocrinology & Metabolism Vol. 2, No. 7 ( 2006-7), p. 374-383
    Details
    In: Nature Clinical Practice Endocrinology & Metabolism, Springer Science and Business Media LLC, Vol. 2, No. 7 ( 2006-7), p. 374-383
    Type of Medium: Online Resource
    ISSN: 1745-8366 , 1745-8374
    URL: Article
    DOI: 10.1038/ncpendmet0197
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2006
    detail.hit.zdb_id: 2489384-5
    detail.hit.zdb_id: 2211780-5
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