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.

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Acknowledgments

The present scientific contribution is dedicated to the 650th anniversary of the foundation of the University of Pécs, Hungary. The authors are grateful to Prof. Zsuzsanna Helyes (Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Hungary) for generously sharing their tail cuff device. The authors are grateful for the expert and excellent technical assistance of Ms. M. Koncsecsko-Gaspar, Ms. A. Mihalffy-Jech, Ms. A. Boka-Kiss, and Ms. I. Orban. Financial support: MMVBT2013-BM (Hungarian Society of Microcirculation and Vascular Biology), 34039/KA-OTKA/13-02 (University of Pecs), 34039/KA-OTKA/13-25 (University of Pecs), OTKA PD100706 (Hungarian Scientific Research Fund).

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Correspondence to Erika Petervari.

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Furedi, N., Miko, A., Aubrecht, B. et al. Regulatory Alterations of Energy Homeostasis in Spontaneously Hypertensive Rats (SHR). J Mol Neurosci 59, 521–530 (2016). https://doi.org/10.1007/s12031-016-0771-2

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Keywords

  • Spontaneously hypertensive rat (SHR)
  • Energy homeostasis
  • Alpha-melanocyte stimulating hormone
  • Neuropeptide Y
  • HS024