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: Nora Furedi, Alexandra Miko, Bianka Aubrecht, Balazs Gaszner, Diana Feller, Ildiko Rostas, Judit Tenk, Szilvia Soos, Marta Balasko, Andras Balogh, Marianna Pap, Erika Petervari
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 59 Issue 4 Pg. 521-30 (Aug 2016) ISSN: 1559-1166 [Electronic] United States
• PMID: 27339773 (Publication Type: Journal Article)

Chemical References

• Agouti-Related Protein
• Hormones
• Neuropeptide Y
• Peptide Fragments
• agouti-related peptide, (Yc(CRFFNAFC)Y)
• alpha-MSH
• Pro-Opiomelanocortin

Topics

• Agouti-Related Protein (pharmacology)
• Animals
• Body Weight
• Energy Metabolism
• Homeostasis
• Hormones (pharmacology)
• Hypertension (metabolism)
• Hypothalamus (drug effects, metabolism)
• Male
• Neuropeptide Y (pharmacology)
• Peptide Fragments (pharmacology)
• Pro-Opiomelanocortin (genetics, metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Wistar
• alpha-MSH (pharmacology)