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Hypothalamic adrenergic receptor changes in the metabolic syndrome of genetically obese (ob/ob) mice.

Authors :
Boundy VA
Cincotta AH
Source :
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2000 Aug; Vol. 279 (2), pp. R505-14.
Publication Year :
2000

Abstract

The genetically, seasonally, and diet-induced obese, glucose-intolerant states in rodents, including ob/ob mice, have each been associated with elevated hypothalamic levels of norepinephrine (NE). With the use of quantitative autoradiography on brain slices of 6-wk-old obese (ob/ob) and lean mice, the adrenergic receptor populations in several hypothalamic nuclei were examined. The binding of [(125)I]iodocyanopindolol to beta(1)- and beta(2)-adrenergic receptors in ob/ob mice was significantly increased in the paraventricular hypothalamic nucleus (PVN) by 30 and 38%, in the ventromedial hypothalamus (VMH) by 23 and 72%, and in the lateral hypothalamus (LH) by 10 and 15%, respectively, relative to lean controls. The binding of [(125)I]iodo-4-hydroxyphenyl-ethyl-aminomethyl-tetralone to alpha(1)-adrenergic receptors was also significantly increased in the PVN (26%), VMH (67%), and LH (21%) of ob/ob mice. In contrast, the binding of [(125)I]paraiodoclonidine to alpha(2)-adrenergic receptors in ob/ob mice was significantly decreased in the VMH (38%) and the dorsomedial hypothalamus (17%) relative to lean controls. This decrease was evident in the alpha(2A)- but not the alpha(2BC)-receptor subtype. Scatchard analysis confirmed this decreased density of alpha(2)-receptors in ob/ob mice. Together with earlier studies, these changes in hypothalamic adrenergic receptors support a role for increased hypothalamic NE activity in the development of the metabolic syndrome of ob/ob mice.

Details

Language :
English
ISSN :
0363-6119
Volume :
279
Issue :
2
Database :
MEDLINE
Journal :
American journal of physiology. Regulatory, integrative and comparative physiology
Publication Type :
Academic Journal
Accession number :
10938239
Full Text :
https://doi.org/10.1152/ajpregu.2000.279.2.R505