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  1. Article ; Online: Thy-1 restricts steatosis and liver fibrosis in steatotic liver disease.

    Blank, Valentin / Karlas, Thomas / Anderegg, Ulf / Wiegand, Johannes / Arnold, Josi / Bundalian, Linnaeus / Le Duc, Gabriela-Diana / Körner, Christiane / Ebert, Thomas / Saalbach, Anja

    Liver international : official journal of the International Association for the Study of the Liver

    2024  

    Abstract: Background and aims: Steatotic liver disease (SLD) is generally considered to represent a hepatic manifestation of metabolic syndrome and includes a disease spectrum comprising isolated steatosis, metabolic dysfunction-associated steatohepatitis, liver ... ...

    Abstract Background and aims: Steatotic liver disease (SLD) is generally considered to represent a hepatic manifestation of metabolic syndrome and includes a disease spectrum comprising isolated steatosis, metabolic dysfunction-associated steatohepatitis, liver fibrosis and ultimately cirrhosis. A better understanding of the detailed underlying pathogenic mechanisms of this transition is crucial for the design of new and efficient therapeutic interventions. Thymocyte differentiation antigen (Thy-1, also known as CD90) expression on fibroblasts controls central functions relevant to fibrogenesis, including proliferation, apoptosis, cytokine responsiveness, and myofibroblast differentiation.
    Methods: The impact of Thy-1 on the development of SLD and progression to fibrosis was investigated in high-fat diet (HFD)-induced SLD wild-type and Thy-1-deficient mice. In addition, the serum soluble Thy-1 (sThy-1) concentration was analysed in patients with metabolic dysfunction-associated SLD stratified according to steatosis, inflammation, or liver fibrosis using noninvasive markers.
    Results: We demonstrated that Thy-1 attenuates the development of fatty liver and the expression of profibrogenic genes in the livers of HFD-induced SLD mice. Mechanistically, Thy-1 directly inhibits the profibrotic activation of nonparenchymal liver cells. In addition, Thy-1 prevents palmitic acid-mediated amplification of the inflammatory response of myeloid cells, which might indirectly contribute to the pronounced development of liver fibrosis in Thy-1-deficient mice. Serum analysis of patients with metabolically associated steatotic liver disease syndrome revealed that sThy-1 expression is correlated with liver fibrosis status, as assessed by liver stiffness, the Fib4 score, and the NAFLD fibrosis score.
    Conclusion: Our data strongly suggest that Thy-1 may function as a fibrosis-protective factor in mouse and human SLD.
    Language English
    Publishing date 2024-05-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2102783-3
    ISSN 1478-3231 ; 1478-3223
    ISSN (online) 1478-3231
    ISSN 1478-3223
    DOI 10.1111/liv.15956
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1632: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: The Emerging Plasticizer Alternative DINCH and Its Metabolite MINCH Induce Oxidative Stress and Enhance Inflammatory Responses in Human THP-1 Macrophages.

    Schaffert, Alexandra / Arnold, Josi / Karkossa, Isabel / Blüher, Matthias / von Bergen, Martin / Schubert, Kristin

    Cells

    2021  Volume 10, Issue 9

    Abstract: The use of the plasticizer bis(2-ethylhexyl)phthalate (DEHP) and other plasticizers in the manufacture of plastic products has been restricted due to adverse health outcomes such as obesity, metabolic syndrome, and asthma, for which inflammation has been ...

    Abstract The use of the plasticizer bis(2-ethylhexyl)phthalate (DEHP) and other plasticizers in the manufacture of plastic products has been restricted due to adverse health outcomes such as obesity, metabolic syndrome, and asthma, for which inflammation has been described to be a driving factor. The emerging alternative plasticizer 1,2-cyclohexanedioic acid diisononyl ester (DINCH) still lacks information regarding its potential effects on the immune system. Here, we investigated the effects of DINCH and its naturally occurring metabolite monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH) on the innate immune response. Human THP-1 macrophages were exposed to 10 nM-10 μM DINCH or MINCH for 4 h, 16 h, and 24 h. To decipher the underlying mechanism of action, we applied an untargeted proteomic approach that revealed xenobiotic-induced activation of immune-related pathways such as the nuclear factor κB (NF-κB) signaling pathway. Key drivers were associated with oxidative stress, mitochondrial dysfunction, DNA damage repair, apoptosis, and autophagy. We verified increased reactive oxygen species (ROS) leading to cellular damage, NF-κB activation, and subsequent TNF and IL-1β release, even at low nM concentrations. Taken together, DINCH and MINCH induced cellular stress and pro-inflammatory effects in macrophages, which may lead to adverse health effects.
    MeSH term(s) Apoptosis/drug effects ; DNA Damage/drug effects ; DNA Repair/drug effects ; Dicarboxylic Acids/metabolism ; Esters/metabolism ; Humans ; Inflammation/drug therapy ; Inflammation/metabolism ; Macrophages/drug effects ; Macrophages/metabolism ; NF-kappa B/metabolism ; Oxidative Stress/drug effects ; Phthalic Acids/metabolism ; Plasticizers/pharmacology ; Proteomics ; Signal Transduction/drug effects ; THP-1 Cells/drug effects ; THP-1 Cells/metabolism
    Chemical Substances Dicarboxylic Acids ; Esters ; NF-kappa B ; Phthalic Acids ; Plasticizers ; phthalic acid (6O7F7IX66E)
    Language English
    Publishing date 2021-09-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10092367
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Di-(2-ethylhexyl) phthalate substitutes accelerate human adipogenesis through PPARγ activation and cause oxidative stress and impaired metabolic homeostasis in mature adipocytes

    Schaffert, Alexandra / Karkossa, Isabel / Ueberham, Elke / Schlichting, Rita / Walter, Katharina / Arnold, Josi / Blüher, Matthias / Heiker, John T. / Lehmann, Jörg / Wabitsch, Martin / Escher, Beate I. / von Bergen, Martin / Schubert, Kristin

    Environment international. 2022 June, v. 164

    2022  

    Abstract: The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe ... ...

    Abstract The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe substitutes gained importance. Focusing on the master regulator of adipogenesis and adipose tissue functionality, the peroxisome proliferator-activated receptor gamma (PPARγ), we evaluated 20 alternative plasticizers as well as their metabolites for binding to and activation of PPARγ and assessed effects on adipocyte lipid accumulation. Among several compounds that showed interaction with PPARγ, the metabolites MINCH, MHINP, and OH-MPHP of the plasticizers DINCH, DINP, and DPHP exerted the highest adipogenic potential in human adipocytes. These metabolites and their parent plasticizers were further analyzed in human preadipocytes and mature adipocytes using cellular assays and global proteomics. In preadipocytes, the plasticizer metabolites significantly increased lipid accumulation, enhanced leptin and adipsin secretion, and upregulated adipogenesis-associated markers and pathways, in a similar pattern to the PPARγ agonist rosiglitazone. Proteomics of mature adipocytes revealed that both, the plasticizers and their metabolites, induced oxidative stress, disturbed lipid storage, impaired metabolic homeostasis, and led to proinflammatory and insulin resistance promoting adipokine secretion. In conclusion, the plasticizer metabolites enhanced preadipocyte differentiation, at least partly mediated by PPARγ activation and, together with their parent plasticizers, affected the functionality of mature adipocytes similar to reported effects of a high-fat diet. This highlights the need to further investigate the currently used plasticizer alternatives for potential associations with obesity and the metabolic syndrome.
    Keywords adipocytes ; adipogenesis ; adipose tissue ; agonists ; environment ; high fat diet ; homeostasis ; humans ; insulin resistance ; leptin ; lipids ; metabolic syndrome ; metabolites ; obesity ; oxidative stress ; pandemic ; peroxisome proliferator-activated receptor gamma ; phthalates ; plasticizers ; proteomics ; secretion
    Language English
    Dates of publication 2022-06
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2022.107279
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3131: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Di-(2-ethylhexyl) phthalate substitutes accelerate human adipogenesis through PPARγ activation and cause oxidative stress and impaired metabolic homeostasis in mature adipocytes.

    Schaffert, Alexandra / Karkossa, Isabel / Ueberham, Elke / Schlichting, Rita / Walter, Katharina / Arnold, Josi / Blüher, Matthias / Heiker, John T / Lehmann, Jörg / Wabitsch, Martin / Escher, Beate I / von Bergen, Martin / Schubert, Kristin

    Environment international

    2022  Volume 164, Page(s) 107279

    Abstract: The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe ... ...

    Abstract The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe substitutes gained importance. Focusing on the master regulator of adipogenesis and adipose tissue functionality, the peroxisome proliferator-activated receptor gamma (PPARγ), we evaluated 20 alternative plasticizers as well as their metabolites for binding to and activation of PPARγ and assessed effects on adipocyte lipid accumulation. Among several compounds that showed interaction with PPARγ, the metabolites MINCH, MHINP, and OH-MPHP of the plasticizers DINCH, DINP, and DPHP exerted the highest adipogenic potential in human adipocytes. These metabolites and their parent plasticizers were further analyzed in human preadipocytes and mature adipocytes using cellular assays and global proteomics. In preadipocytes, the plasticizer metabolites significantly increased lipid accumulation, enhanced leptin and adipsin secretion, and upregulated adipogenesis-associated markers and pathways, in a similar pattern to the PPARγ agonist rosiglitazone. Proteomics of mature adipocytes revealed that both, the plasticizers and their metabolites, induced oxidative stress, disturbed lipid storage, impaired metabolic homeostasis, and led to proinflammatory and insulin resistance promoting adipokine secretion. In conclusion, the plasticizer metabolites enhanced preadipocyte differentiation, at least partly mediated by PPARγ activation and, together with their parent plasticizers, affected the functionality of mature adipocytes similar to reported effects of a high-fat diet. This highlights the need to further investigate the currently used plasticizer alternatives for potential associations with obesity and the metabolic syndrome.
    MeSH term(s) Adipocytes/metabolism ; Adipogenesis ; Diethylhexyl Phthalate/metabolism ; Diethylhexyl Phthalate/toxicity ; Homeostasis ; Humans ; Lipids ; Obesity/metabolism ; Oxidative Stress ; PPAR gamma/metabolism ; Phthalic Acids ; Plasticizers/metabolism ; Plasticizers/toxicity
    Chemical Substances Lipids ; PPAR gamma ; Phthalic Acids ; Plasticizers ; phthalic acid (6O7F7IX66E) ; Diethylhexyl Phthalate (C42K0PH13C)
    Language English
    Publishing date 2022-05-06
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2022.107279
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3131: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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