Journal Article

Regulatory Alterations of Energy Homeostasis in Spontaneously Hypertensive Rats (SHR)

Soos, Szilvia, Tenk, Judit, Petervari, Erika, Furedi, Nora, Miko, Alexandra, Rostas, Ildiko, Balasko, Marta, Aubrecht, Bianka, Feller, Diana, Pap, Marianna, Gaszner, Balazs, Balogh, Andras

2016

Overview

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.

• Publisher: Springer US,Springer Nature B.V
• Subject: Agouti-Related Protein - pharmacology / alpha-MSH - pharmacology / Animals / Biomedical and Life Sciences / Biomedicine / Blood pressure / Body Weight / Cell Biology / Energy / Energy Metabolism / Gene expression / Homeostasis / Hormones - pharmacology / Hypertension / Hypertension - metabolism / Hypothalamus / Hypothalamus - drug effects / Hypothalamus - metabolism / Kinases / Laboratory animals / Male / Medical schools / Metabolism / Neurochemistry / Neurology / Neuropeptide Y - pharmacology / Neuropeptides / Neurosciences / Peptide Fragments - pharmacology / Peptides / Pro-Opiomelanocortin - genetics / Pro-Opiomelanocortin - metabolism / Proteomics / Rats / Rats, Inbred SHR / Rats, Wistar