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

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 [125I]iodocyanopindolol to β1- and β2-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 [125I]iodo-4-hydroxyphenyl-ethyl-aminomethyl-tetralone to α1-adrenergic receptors was also significantly increased in the PVN (26%), VMH (67%), and LH (21%) of ob/ ob mice. In contrast, the binding of [125I]paraiodoclonidine to α2-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 α2A- but not the α2BC-receptor subtype. Scatchard analysis confirmed this decreased density of α2-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/ obmice.