OBESITY-PRONE AND OBESITY-RESISTANT RATS DIFFER IN THEIR BRAIN [H-3] PARAMINOCLONIDINE BINDING

Half the rats fed a high-energy diet develop diet-induced obesity (DIO); the remainder are diet-resistant (DR). Since α-adrenoceptors modulate both food intake and body weight, this study was conducted to identify potential differences in brain α-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 α-adrenoceptors was studied in these 12 rats by receptor autoradigraphy using 1 nM [3H]prazosin (PRZ; α1-) and 1 nM [3H]paraminoclonidine (PAC; α2-). 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, medial eminence and medial dorsal thalamic N. Although it is unclear whether this widespread decrease in [3H]PAC binding implicates brain α2-adrenoceptors 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. © 1990.