TNFα is a key trigger of inflammation in diet-induced non-obese MASLD in mice
Tumor necrosis factor alpha (TNFα) is thought to be a critical factor in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we determined the effects of a treatment with the anti-TNFα antibody infliximab and a genetic deletion of TNFα, respectively, in the dev...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231723002719 |
| _version_ | 1797689312379142144 |
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| author | Katharina Burger Finn Jung Anja Baumann Annette Brandt Raphaela Staltner Victor Sánchez Ina Bergheim |
| author_facet | Katharina Burger Finn Jung Anja Baumann Annette Brandt Raphaela Staltner Victor Sánchez Ina Bergheim |
| author_sort | Katharina Burger |
| collection | DOAJ |
| description | Tumor necrosis factor alpha (TNFα) is thought to be a critical factor in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we determined the effects of a treatment with the anti-TNFα antibody infliximab and a genetic deletion of TNFα, respectively, in the development of non-obese diet-induced early metabolic dysfunction-associated steatohepatitis (MASH) in mice. The treatment with infliximab improved markers of liver damage in mice with pre-existing early MASH. In TNFα−/− mice, the development of early signs of MASH and insulin resistance was significantly attenuated compared to wild-type animals. While mRNA expression of proinflammatory cytokines like interleukin 1β (Il1b) and interleukin 6 (Il6) were significantly lower in livers of MASH-diet-fed TNFα−/− mice compared to wild-type mice with early MASH, markers of intestinal barrier function were similarly impaired in both MASH-diet-fed groups compared to controls. Our data suggest that TNFα is a key regulator of hepatic inflammation and insulin resistance associated with the development of early non-obese MASH. |
| first_indexed | 2024-03-12T01:43:53Z |
| format | Article |
| id | doaj.art-ed30d64827f2420fb26ddddcf861f88a |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-03-12T01:43:53Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-ed30d64827f2420fb26ddddcf861f88a2023-09-10T04:24:12ZengElsevierRedox Biology2213-23172023-10-0166102870TNFα is a key trigger of inflammation in diet-induced non-obese MASLD in miceKatharina Burger0Finn Jung1Anja Baumann2Annette Brandt3Raphaela Staltner4Victor Sánchez5Ina Bergheim6Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, AustriaDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, AustriaDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, AustriaDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, AustriaDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, AustriaDepartment of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, AustriaCorresponding author. University of Vienna, Department of Nutritional Sciences, Molecular Nutritional Science, Josef-Holaubek-Platz 2, (UZA II), A-1090, Wien, Austria.; Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, AustriaTumor necrosis factor alpha (TNFα) is thought to be a critical factor in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we determined the effects of a treatment with the anti-TNFα antibody infliximab and a genetic deletion of TNFα, respectively, in the development of non-obese diet-induced early metabolic dysfunction-associated steatohepatitis (MASH) in mice. The treatment with infliximab improved markers of liver damage in mice with pre-existing early MASH. In TNFα−/− mice, the development of early signs of MASH and insulin resistance was significantly attenuated compared to wild-type animals. While mRNA expression of proinflammatory cytokines like interleukin 1β (Il1b) and interleukin 6 (Il6) were significantly lower in livers of MASH-diet-fed TNFα−/− mice compared to wild-type mice with early MASH, markers of intestinal barrier function were similarly impaired in both MASH-diet-fed groups compared to controls. Our data suggest that TNFα is a key regulator of hepatic inflammation and insulin resistance associated with the development of early non-obese MASH.http://www.sciencedirect.com/science/article/pii/S2213231723002719Fatty liverMASHEndotoxinInsulin resistanceIntestinal barrier |
| spellingShingle | Katharina Burger Finn Jung Anja Baumann Annette Brandt Raphaela Staltner Victor Sánchez Ina Bergheim TNFα is a key trigger of inflammation in diet-induced non-obese MASLD in mice Redox Biology Fatty liver MASH Endotoxin Insulin resistance Intestinal barrier |
| title | TNFα is a key trigger of inflammation in diet-induced non-obese MASLD in mice |
| title_full | TNFα is a key trigger of inflammation in diet-induced non-obese MASLD in mice |
| title_fullStr | TNFα is a key trigger of inflammation in diet-induced non-obese MASLD in mice |
| title_full_unstemmed | TNFα is a key trigger of inflammation in diet-induced non-obese MASLD in mice |
| title_short | TNFα is a key trigger of inflammation in diet-induced non-obese MASLD in mice |
| title_sort | tnfα is a key trigger of inflammation in diet induced non obese masld in mice |
| topic | Fatty liver MASH Endotoxin Insulin resistance Intestinal barrier |
| url | http://www.sciencedirect.com/science/article/pii/S2213231723002719 |
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