Decreased central and peripheral catecholaminergic activation in obese zucker rats

Karel Pacak, Richard Mc carty, Miklos Palkovits, Giovanni Cizza, Irwin J. Kopin, David S. Goldstein, George P. Chrousos

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Abstract

The Zucker rat is an animal model of autosomal recessive obesity characterized by excessive hypothalamic-pituitary-adrenal (HPA) axis and parasympathetic activities and deficient sympathetic outflow. Alterations in norepinephrine (NE) release, reuptake, and metabolism in the hypothalamic paraventricular nucleus (PVN) could also contribute to dysregulation of the HPA axis in obese Zucker rats via effects on corticotropin-releasing hormone neurons or could be secondary to some other primary defect. The present study assessed whether the obese phenotype defect. The present study assessed whether the obese phenotype (fa/fa) compared to the lean phenotype (Fa/?) of this strain was also associated with alterations in basal and immobilization (IMMO) stress-induced noradrenergic activation in the PVN, using in vivo microdialysis. To evaluate concurrent activity of the peripheral sympathetic nervous system and the HPA axis, we also measured plasma concentrations of catecholamines, ACTH, and corticosterone. IMMO-induced increases in PVN NE levels were significantly lower in obese Zucker rats, as were elevations in plasma concentrations of dihydroxyphenylglycol and epinephrine. Basal and IMMO-stimulated plasma ACTH concentrations were similar in obese and lean rats. Basal plasma corticosterone concentrations were also similar in obese and lean rats; however, IMMO-stimulated corticosterone levels were significantly greater in obese than in lean animals. Basal plasma free corticosterone levels, measured by ultrafiltration, were significantly higher in obese than in lean rats, confirming the state of chronic hypercorticosteronism in these animals. These findings indicate that obese Zucker rats have diminished central noradrenergic and peripheral sympathetic nervous system responses to IMMO stress along with a chronically hyperactive HPA axis. We suggest that defective regulation of PVN NE reflects and contributes to the development and/or maintenance of obesity in Zucker rats via central hypoactivity of the sympathetic system. The hypercorticosteronism of these animals, apparently sustained by some nonadrenergic stimulatory input, might participate in the suppression of the sympathetic system.

Original languageEnglish
Pages (from-to)4360-4367
Number of pages8
JournalEndocrinology
Volume136
Issue number10
DOIs
Publication statusPublished - Oct 1995

ASJC Scopus subject areas

  • Endocrinology

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    Pacak, K., Mc carty, R., Palkovits, M., Cizza, G., Kopin, I. J., Goldstein, D. S., & Chrousos, G. P. (1995). Decreased central and peripheral catecholaminergic activation in obese zucker rats. Endocrinology, 136(10), 4360-4367. https://doi.org/10.1210/endo.136.10.7664655