We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The Influence of the FFAR4 Agonist TUG-891 on Liver Steatosis in ApoE-Knockout Mice.
- Authors
Kiepura, Anna; Suski, Maciej; Stachyra, Kamila; Kuś, Katarzyna; Czepiel, Klaudia; Wiśniewska, Anna; Ulatowska-Białas, Magdalena; Olszanecki, Rafał
- Abstract
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.
- Subjects
NON-alcoholic fatty liver disease; FATTY liver; FATTY degeneration; FREE fatty acids; LIVER; CORONARY disease
- Publication
Cardiovascular Drugs & Therapy, 2024, Vol 38, Issue 4, p667
- ISSN
0920-3206
- Publication type
Article
- DOI
10.1007/s10557-023-07430-7