MASLD is related to impaired alcohol dehydrogenase (ADH) activity and elevated blood ethanol levels: Role of TNFα and JNK
- Autor(en)
- Katharina Burger, Finn Jung, Katharina Staufer, Ruth Ladurner, Michael Trauner, Anja Baumann, Annette Brandt, Ina Bergheim
- Abstrakt
Elevated fasting ethanol levels in peripheral blood frequently found in metabolic dysfunction-associated steatohepatitis (MASLD) patients even in the absence of alcohol consumption are discussed to contribute to disease development. To test the hypothesis that besides an enhanced gastrointestinal synthesis a diminished alcohol elimination through alcohol dehydrogenase (ADH) may also be critical herein, we determined fasting ethanol levels and ADH activity in livers and blood of MASLD patients and in wild-type ± anti-TNFα antibody (infliximab) treated and TNFα
-/- mice fed a MASLD-inducing diet. Blood ethanol levels were significantly higher in patients and wild-type mice with MASLD while relative ADH activity in blood and liver tissue was significantly lower compared to controls. Both alterations were significantly attenuated in MASLD diet-fed TNFα
-/- mice and wild-type mice treated with infliximab. Moreover, alcohol elimination was significantly impaired in mice with MASLD. In in vitro models, TNFα but not IL-1β or IL-6 significantly decreased ADH activity. Our data suggest that elevated ethanol levels in MASLD patients are related to TNFα-dependent impairments of ADH activity.
- Organisation(en)
- Department für Ernährungswissenschaften
- Externe Organisation(en)
- Medizinische Universität Wien, Universitätsklinikum Tübingen
- Journal
- Redox biology
- Band
- 71
- ISSN
- 2213-2317
- DOI
- https://doi.org/10.1016/j.redox.2024.103121
- Publikationsdatum
- 03-2024
- Peer-reviewed
- Ja
- ÖFOS 2012
- 303009 Ernährungswissenschaften
- Schlagwörter
- ASJC Scopus Sachgebiete
- Organic Chemistry
- Link zum Portal
- https://ucrisportal.univie.ac.at/de/publications/5e67128a-fe8e-4193-976c-83165245df17