Abstract
A role for the kinin B1 receptor in energy-homeostatic processes was implicated in previous studies; notably, the studies where kinin B1 receptor knockout mice (B1-/-) were shown to have impaired adiposity, impaired leptin and insulin production, lower feed efficiency, protection from liver steatosis and diet-induced obesity when fed a high fat diet (HFD). In particular, in a model where the B1 receptor is expressed exclusively in the adipose tissue, it rescues the plasma insulin concentration and the weight gain seen in wild type mice. Taking into consideration that leptin participates in the formation of hypothalamic nuclei, which modulate energy expenditure, and feeding behavior, we hypothesized that these brain regions could also be altered in B1-/- mice. We observed for the first time a difference in the gene expression pattern of cocaine and amphetamine related transcript (CART) in the (lateral hypothalamic area (LHA) resulting from the deletion of the kinin B1 receptor gene. The correlation between CART expression in the LHA and the thwarting of diet-induced obesity corroborates independent correlations between CART and obesity. Furthermore, it seems to indicate that the mechanism underlying the ‘lean’ phenotype of B1-/- mice does not stem solely from changes in peripheral tissues but may also receive contributions from changes in the hypothalamic machinery involved in energy homeostasis processes.
This work was supported by grants from Conselho Nacional de Desenvolvimento Científico Tecnológico (CNPq, 134730/2006-2). HAMT, VD’A, LEM, JCB, and JBP are recipients of fellowships from CNPq, Brazil. GFB and VMS is a recipient of a Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) fellowship. Financial support from FAPESP to JBP (2008)/06676-8) and to JCB (2004)/13849-5) is acknowledged. RSC is a recipient of an Associação Beneficente de Coleta de Sangue/Universidade Federal de São Paulo (COLSAN-UNIFESP) fellowship.
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This paper was originally submitted to the Highlight Issue in connection with the ‘Kinin 2012’ symposium (March 2013 issue).
References
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