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
Conclusion
Pharmacological stimulation of FFAR4 may represent a promising lead in the search for drugs that inhibit NAFLD.
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).