Lack of kinin B-1 receptor potentiates leptin action in the liver

Author(s)

Fonseca, Raphael Gomes ^[1] ; Sales, Vicencia Micheline ^[1] ; Ropelle, Eduardo ^[2] ; Barros, Carlos Castilho ^[1] ; Oyama, Lila ^[3] ; Iuki Ihara, Silvia Saiuli ^[4] ; Abdalla Saad, Mario Jose ^[5] ; Araujo, Ronaldo Carvalho ^[1] ; Pesquero, Joao Bosco ^[1]

Affiliation

^[1] Fed Univ Sao Paulo UNIFESP EPM, Dept Biophys, BR-04039032 Sao Paulo - Brazil

^[2] State Univ Campinas UNICAMP, Sch Appl Sci, Sao Paulo - Brazil

^[3] Fed Univ Sao Paulo UNIFESP EPM, Dept Physiol, BR-04039032 Sao Paulo - Brazil

^[4] Fed Univ Sao Paulo UNIFESP EPM, Dept Pathol, BR-04039032 Sao Paulo - Brazil

^[5] State Univ Campinas UNICAMP, Dept Internal Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF MOLECULAR MEDICINE-JMM; v. 91, n. 7, p. 851-860, JUL 2013.
• Web of Science Citations: 10

Abstract

Kinins B-1 and B-2 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 (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 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. 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 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. (AU)

• FAPESP's process: 08/06676-8 - Cellular and molecular biology of the kallikrein-kinin and renin-angiotensin systems
• Grantee: João Bosco Pesquero
• Support Opportunities: Research Projects - Thematic Grants