Hypothalamic adrenergic receptor changes in the metabolic syndrome of genetically obese (ob/ob) mice.
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.
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Ergo Science Corporation, North Andover, MA 01845, USA.
Cincotta
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D000818:Animals; D001345:Autoradiography; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D066298:In Vitro Techniques; D020120:Iodocyanopindolol / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012016:Reference Values; D044024:Tetralones; D014018:Tissue Distribution
D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D044024:Tetralones; C053113:4-iodoclonidine; D020120:Iodocyanopindolol; C048008:2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl)tetralone; D003000:Clonidine