Kinins B1 and B2 receptors (B1R and B2R) are classically associated with
inflammation, but our group has recently demonstrated new roles for B1R in metabolism using a knockout model (B1 (-/-)). B1 (-/-) mice display improvement on
leptin and
insulin sensitivity and is protected from high fat diet (HFD)-induced
obesity. Here, we evaluate the hepatic effects of the B1R ablation and its role on hepatic function. Despite no expression of hepatic B1R, HFD-induced hepatic
lipid accumulation was lower than in control animals. B1 (-/-) mice also presented lower hepatic lipogenesis and SCD1
protein content in the liver. When stimulated with exogenous
leptin, B1 (-/-) mice exhibited increased hepatic pJAK2. Similarly,
leptin signaling was enhanced in the liver of ob/ob-B1 (-/-) mice, as demonstrated by increased levels of pSTAT3 compared to ob/ob. Plasma concentrations of
intercellular adhesion molecule 1,
fetuin A,
leukemia inhibitory factor, tissue inhibitor of metalloprotease-1,
resistin, and
oncostatin M were reduced in B1 (-/-). Finally, B1 (-/-) mice have increased gene expression of hepatic B2 receptor, but no difference in
leptin receptor expression. Our results show that B1 (-/-) mice are protected from
non-alcoholic fatty liver disease (
NAFLD) after HFD treatment. Since B1R expression was not observed in the liver after HFD, we propose that the cross talk between the adipose tissue and the liver, mainly through
leptin, is an important factor contributing to the observed results. Besides that, several other inflammatory mediators already correlated with
NAFLD or liver function were found to be altered in our model. Taken together, our data suggest that B1R plays an important role in hepatic steatosis development.