title: Regulation of expression of relaxin-3 and its receptor RXFP3 in the brain of diet-induced obese rats.
abstract: An animal model closely related to human obesity is diet-induced obesity in Sprague-Dawley rats. These rats placed on a high-energy (HE) diet show wide distribution in body weight gain with a subset of animals developing diet-induced obesity (DIO) and the remaining animals showing a diet-resistant (DR) phenotype. Once obesity is established, DIO rats strongly defend their increased body weight against caloric restriction. There is evidence that neuropeptide relaxin-3 is involved in food intake regulation, but the levels of expression of relaxin-3 and its receptor have not been yet demonstrated in the DIO model. The present study investigated the brain expression of relaxin-3 and its cognate receptor RXFP3 in DIO and DR rats maintained on an HE diet since weaning. Expression of relaxin-3 and RXFP3 mRNAs was assessed by in situ hybridization in ad libitum, food-deprived (12 h) and refed (1 h) feeding states. The levels of expression of relaxin-3 in the medial portion of the nucleus incertus (NI) were higher in the DIO rats compared to the DR rats in the ad libitum-fed state. Food deprivation increased the levels of expression of relaxin-3 in the medial NI in DR but not DIO rats. The stronger expression of relaxin-3 in the ad libitum-fed state in the DIO rats was accompanied by low expression of the RXFP3 receptor in the paraventricular hypothalamic nucleus (PVN), supraoptic nucleus, central amygdala (CeA), NI, and nucleus of the solitary tract (NTS). Refeeding increased expression of RXFP3 in the paraventricular thalamic nucleus, parvocellular PVN, CeA, NI, and NTS in the DIO rats. These results provide evidence that DIO rats show a constitutive increase in relaxin-3 expression in the medial NI and that refeeding after food deprivation may enhance the orexigenic effects of relaxin-3 in DIO rats by rapid upregulation of the expression of RXFP3 in the specific brain regions involved in food intake regulation.
authors.affiliation: Faculté de Médecine, Département Psychiatrie et Neurosciences, Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, QC G1V 4G5, Canada.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lenglos
authors.affiliation: Faculté de Médecine, Département Psychiatrie et Neurosciences, Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, QC G1V 4G5, Canada.
authors.forename: Arojit
authors.initials: A
authors.lastname: Mitra
authors.affiliation: Faculté de Médecine, Département Psychiatrie et Neurosciences, Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, QC G1V 4G5, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Guèvremont
authors.affiliation: Faculté de Médecine, Département Psychiatrie et Neurosciences, Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, QC G1V 4G5, Canada. Electronic address: Elena.Timofeeva@fmed.ulaval.ca.
authors.forename: Elena
authors.initials: E
authors.lastname: Timofeeva
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation; D005941:Glucokinase / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D012065:Relaxin / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D009419:Nerve Tissue Proteins; C466742:RLN3 protein, rat; D012333:RNA, Messenger; C577472:RXFP3 protein, rat; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012065:Relaxin; D005941:Glucokinase; D003345:Corticosterone
keywords: Diet; Obesity; RXFP3; Relaxin-3