Curta administração de GW501516 melhora o estado inflamatório do tecido adiposo branco, o dano hepático e a inflamação renal de camundongos alimentados com dieta rica em frutose

Abstract

High-activation of ACE/AT1r axis is closely linked to metabolix syndrome and low-grade inflammation state. Fructose administration in water or in diet has been proposed as a model to study the high-activity of this axis and AT1r-related inflammatory pathways. In this view, we aimed to evaluate if GW501516 administration could decrease the high-activation of ACE/AT1r axis and consequently fructose damage. To this males mice C57Bl/6 were fed a high-fructose diet (47%) during eight weeks or standard-chow diet. After eight weeks, the groups were randomly divided to start treatment with GW501516, totaling four experimental groups. Animals treated with GW501516 presented an improvement of systolic blood pressure and in urinary parameters, as proteinuria and uric acid. Also was verified an improvement in plasmatic triglycerides and uric acid. In white adipose tissue, GW501516 was able to decrease the components of this axis and improved inflammation as well. In liver, it was not found differences in axis, but JAK2 phosphorylation AT1r-dependent was decreased and consequently it was found a diminished activations of hepatic stellate cells. In addition, proteins and genes related to β-oxidation were increased with GW501516 and those related to lipogenesis de novo, were diminished, improving hepatic parenchyma. Kidneys presented an improvement of inflammation state, although it was not found differences in axis with treatment. Also, it was not found differences in gene and protein expression in relation to anti-oxidants proteins. These results show that short-administration of GW501516 could alleviate inflammatory effects and hepatic steatosis caused by high fructose diet, suggesting that GW501516 could be a new therapeutic option to treat the high activation of ACE/AT1r axis