The Influence of the FFAR4 Agonist TUG-891 on Liver Steatosis in ApoE-Knockout Mice.

Autor: Kiepura A; Department of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Krakow, Poland., Suski M; Department of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Krakow, Poland., Stachyra K; Department of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Krakow, Poland., Kuś K; Department of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Krakow, Poland., Czepiel K; Department of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Krakow, Poland., Wiśniewska A; Department of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Krakow, Poland., Ulatowska-Białas M; Department of Pathomorphology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Krakow, Poland., Olszanecki R; Department of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Krakow, Poland. rafal.olszanecki@uj.edu.pl.
Jazyk: angličtina
Zdroj: Cardiovascular drugs and therapy [Cardiovasc Drugs Ther] 2024 Aug; Vol. 38 (4), pp. 667-678. Date of Electronic Publication: 2023 Jan 27.
DOI: 10.1007/s10557-023-07430-7
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: