title: Regulatory Alterations of Energy Homeostasis in Spontaneously Hypertensive Rats (SHR).
abstract: Spontaneously hypertensive rats (SHR) have high sympathetic tone and progressive hypertension. Chronic calorie-restriction prevents hypertension. Their food intake (FI) and body weight are lower than in normotensive (NT) controls, even on a high-fat diet, suggesting a dysregulation of energy homeostasis. We assumed enhanced activity of hypothalamic anorexigenic melanocortins and diminished tone of orexigenic neuropeptide Y (NPY) in the background. FI of male SHR and NT Wistar rats was recorded in a FeedScale system upon intracerebroventricular injection of NPY, melanocortin ligands alpha-melanocyte-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP) or during a 7-day intracerebroventricular infusion of melanocortin antagonist HS024. Alpha-MSH, NPY, and AgRP immunoreactivities were semi-quantified in the arcuate (ARC) and paraventricular (PVN) nuclei of the hypothalamus in NT vs. SHR. Proopiomelanocortin gene expression was also assessed by quantitative RT-PCR in the ARC. Melanocortin-induced anorexia was stronger, FI induced by NPY or HS024 was smaller and delayed in SHR. Cellular alpha-MSH-specific signal density was higher in the ARC of SHR as evaluated by immunofluerescence, which was supported by PCR data. In the PVN, no differences in alpha-MSH-, NPY-, or AgRP-immunosignal were observed. Our results suggest that a higher melanocortin production/responsiveness and lower NPY responsiveness may contribute to the body weight dysregulation of SHR.
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pecs, 12 Szigeti str., Pecs, 7624, Hungary.
authors.forename: Nora
authors.initials: N
authors.lastname: Furedi
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pecs, 12 Szigeti str., Pecs, 7624, Hungary.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Miko
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pecs, 12 Szigeti str., Pecs, 7624, Hungary.
authors.forename: Bianka
authors.initials: B
authors.lastname: Aubrecht
authors.affiliation: Department of Anatomy, Medical School, University of Pecs, Pecs, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Gaszner
authors.affiliation: Department of Pharmaceutical Biotechnology, Medical School, University of Pecs, Pecs, Hungary.
authors.forename: Diana
authors.initials: D
authors.lastname: Feller
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pecs, 12 Szigeti str., Pecs, 7624, Hungary.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Rostas
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pecs, 12 Szigeti str., Pecs, 7624, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Tenk
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pecs, 12 Szigeti str., Pecs, 7624, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Soos
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pecs, 12 Szigeti str., Pecs, 7624, Hungary.
authors.forename: Marta
authors.initials: M
authors.lastname: Balasko
authors.affiliation: Department of Medical Biology, Medical School, University of Pecs, Pecs, Hungary.
authors.forename: Andras
authors.initials: A
authors.lastname: Balogh
authors.affiliation: Department of Medical Biology, Medical School, University of Pecs, Pecs, Hungary.
authors.forename: Marianna
authors.initials: M
authors.lastname: Pap
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pecs, 12 Szigeti str., Pecs, 7624, Hungary. erika.petervari@aok.pte.hu.
authors.forename: Erika
authors.initials: E
authors.lastname: Petervari
mesh_terms: D054369:Agouti-Related Protein / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D004734:Energy Metabolism; D006706:Homeostasis; D006728:Hormones / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D054369:Agouti-Related Protein; D006728:Hormones; D009478:Neuropeptide Y; D010446:Peptide Fragments; C412618:agouti-related peptide, (Yc(CRFFNAFC)Y); D000521:alpha-MSH; D011333:Pro-Opiomelanocortin
keywords: Alpha-melanocyte stimulating hormone; Energy homeostasis; HS024; Neuropeptide Y; Spontaneously hypertensive rat (SHR)