Obesity-prone and -resistant rats differ in their brain [3H]paraminoclonidine binding

Half the rats fed a high-energy diet develop diet-induced obesity (DIO); the remainder are diet-resistant (DR). Since alpha-adrenoceptors modulate both food intake and body weight, this study was conducted to identify potential differences in brain alpha-receptor binding which might predispose some animals to become DIO (DIO-prone) and others DR (DR-prone) when fed a high energy diet. DIO-prone rats can be prospectively identified by high and DR-prone rats by a low plasma norepinephrine (NE) response to i.v. glucose. Here 28 chow-fed rats were tested for glucose-induced NE release and the 6 highest and 6 lowest plasma NE responders were identified as being most likely to be DIO- and DR-prone, respectively. Binding to brain alpha-adrenoceptors was studied in these 12 rats by receptor autoradiography using 1 nM [3H]prazosin (PRZ; alpha 1-) and 1 nM [3H]paraminoclonidine (PAC; alpha 2-). There were no differences in [3H]PRZ binding in any of 18 brain areas examined. However, DIO-prone [3H]PAC binding was only 14-39% of DR-prone levels in 9 areas including 4 amygdalar nuclei, the lateral area, dorso- and ventromedial nuclei of the hypothalamus, median eminence and medial dorsal thalamic n. Although it is unclear whether this widespread decrease in [3H]PAC binding implicates brain alpha 2-adrenoceptors in the pathophysiology of DIO, it does correlate with a phenotypic marker (increase glucose-induced NE release) which predicts the subsequent development of DIO on a high-energy diet.