The Influence of the FFAR4 Agonist TUG-891 on Liver Steatosis in ApoE-Knockout Mice
العنوان: | The Influence of the FFAR4 Agonist TUG-891 on Liver Steatosis in ApoE-Knockout Mice |
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المؤلفون: | Anna Kiepura, Maciej Suski, Kamila Stachyra, Katarzyna Kuś, Klaudia Czepiel, Anna Wiśniewska, Magdalena Ulatowska-Białas, Rafał Olszanecki |
المصدر: | Cardiovascular Drugs and Therapy. |
بيانات النشر: | Springer Science and Business Media LLC, 2023. |
سنة النشر: | 2023 |
مصطلحات موضوعية: | Pharmacology, Pharmacology (medical), General Medicine, Cardiology and Cardiovascular Medicine |
الوصف: | Background Nonalcoholic fatty liver disease (NAFLD) constitutes an independent risk factor for the development of coronary heart disease. Low-grade inflammation has been shown to play an important role in the development of atherosclerosis and NAFLD. Free fatty acid receptor 4 (FFAR4/GPR120), which is involved in damping inflammatory reactions, may represent a promising target for the treatment of inflammatory diseases. Our objective was to evaluate the effect of TUG-891, the synthetic agonist of FFAR4/GPR120, on fatty liver in vivo. Methods The effect of TUG-891 on fatty liver was investigated in apoE−/− mice fed a high-fat diet (HFD), using microscopic, biochemical, molecular, and proteomic methods. Results Treatment with TUG-891 inhibited the progression of liver steatosis in apoE−/− mice, as evidenced by histological analysis, and reduced the accumulation of TG in the liver. This action was associated with a decrease in plasma AST levels. TUG-891 decreased the expression of liver genes and proteins involved in de novo lipogenesis (Srebp-1c, Fasn and Scd1) and decreased the expression of genes related to oxidation and uptake (Acox1, Ehhadh, Cd36, Fabp1). Furthermore, TUG-891 modified the levels of selected factors related to glucose metabolism (decreased Glut2, Pdk4 and Pklr, and increased G6pdx). Conclusion Pharmacological stimulation of FFAR4 may represent a promising lead in the search for drugs that inhibit NAFLD. Graphical abstract |
تدمد: | 1573-7241 0920-3206 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9b5105ddc24adf01a08bb5ceb32b2db9 https://doi.org/10.1007/s10557-023-07430-7 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....9b5105ddc24adf01a08bb5ceb32b2db9 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15737241 09203206 |
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