Kinin B1 receptor gene ablation affects hypothalamic CART production^b

Abstract

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.

Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice

“…Recently, our group found that CART mRNA expression is elevated in the lateral hypothalamic area of B1KO mice. 24 Even though B1KO and B1B2KO mice show similarities in some aspects of metabolism, expression of CART seems to be different in the two strains. However, it should be taken into account that we analyzed expression of CART in the whole hypothalamus of B1B2KO mice, and not only in the lateral hypothalamic area, which may have contributed to the observed lack of differences.…”