Lack of kinin B1 receptor potentiates leptin action in the liver

• Published in: Journal of molecular medicine (Berlin, Germany) Germany), 2013-07, Vol.91 (7), p.851-860
• Main Authors: Fonseca, Raphael Gomes, Sales, Vicencia Micheline, Ropelle, Eduardo, Barros, Carlos Castilho, Oyama, Lila, Ihara, Silvia Saiuli Iuki, Saad, Mário Jose Abdalla, Araújo, Ronaldo Carvalho, Pesquero, João Bosco
• Format: Article
• Language: English
• Subjects: Adipokines - blood; Animals; Biomedical and Life Sciences; Biomedicine; Diet, High-Fat; Fatty Liver - metabolism; Human Genetics; Internal Medicine; Leptin - metabolism; Liver - metabolism; Male; Mice; Mice, Knockout; Molecular Medicine; Non-alcoholic Fatty Liver Disease; Original Article; Receptor, Bradykinin B1 - deficiency; Receptor, Bradykinin B1 - genetics; Receptor, Bradykinin B2 - metabolism; Receptors, Leptin - metabolism; Stearoyl-CoA Desaturase - metabolism
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-013-1004-6

Kinins B 1 and B 2 receptors (B 1 R and B 2 R) are classically associated with inflammation, but our group has recently demonstrated new roles for B 1 R in metabolism using a knockout model (B 1 −/− ). B 1 −/− 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 B 1 R ablation and its role on hepatic function. Despite no expression of hepatic B 1 R, HFD-induced hepatic lipid accumulation was lower than in control animals. B 1 −/− mice also presented lower hepatic lipogenesis and SCD1 protein content in the liver. When stimulated with exogenous leptin, B 1 −/− mice exhibited increased hepatic pJAK2. Similarly, leptin signaling was enhanced in the liver of ob/ob –B 1 −/− 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 B 1 −/− . Finally, B 1 −/− mice have increased gene expression of hepatic B 2 receptor, but no difference in leptin receptor expression. Our results show that B 1 −/− mice are protected from non-alcoholic fatty liver disease (NAFLD) after HFD treatment. Since B 1 R 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 B 1 R plays an important role in hepatic steatosis development.