title: Kinin B1 receptor gene ablation affects hypothalamic CART productionb.
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.
authors.affiliation: Biophysics Department, Universidade Federal de S a o Paulo UNIFESP, Rua Pedro de Toledo 669 9 o andar, Vila Clementino, 04039-002, Sao Paulo, SP, Brazil.
authors.forename: Hugo A M
authors.initials: HA
authors.lastname: Torres
authors.forename: Fabiana
authors.initials: F
authors.lastname: Louise Motta
authors.forename: Vicencia Micheline
authors.initials: VM
authors.lastname: Sales
authors.forename: Carolina
authors.initials: C
authors.lastname: Batista
authors.forename: Joelcimar M
authors.initials: JM
authors.lastname: da Silva
authors.forename: Thiago
authors.initials: T
authors.lastname: Vignoli
authors.forename: Gabriela F
authors.initials: GF
authors.lastname: Barnabé
authors.forename: Francine O
authors.initials: FO
authors.lastname: Goeldner
authors.forename: Vânia
authors.initials: V
authors.lastname: D'Almeida
authors.forename: Jackson C
authors.initials: JC
authors.lastname: Bittencourt
authors.forename: Rita
authors.initials: R
authors.lastname: Sinigaglia-Coimbra
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Luiz Eugênio A M
authors.initials: LE
authors.lastname: Mello
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D002149:Energy Intake / Q000502:physiology; D007026:Hypothalamic Area, Lateral / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007705:Kinins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D007705:Kinins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein