Altered α₁-adrenoceptor binding in intact and adrenalectomized obese Zucker rats ( fa fa)

While many autonomic and metabolic defects associated with genetic obesity in the Zucker rat are corrected by adrenalectomy (Adx), brain adrenoceptor function has not been examined in this context. Here, 3 weeks after Adx or sham surgery, brains of 11 weeks old lean ( Fa Fa) and obese ( fa fa) male Zucker rats were assayed for α₁-([³H]prazosin; [³H]PRZ) and α₂-adrenoceptor ([³H]paraminoclonidine; [³H]PAC) binding by autoradiography. By genotype, obese rats had 19-256% higher [³H]PRZ binding than lean rats in the amygdala (central [ACN], basolateral [ABL], basomedial [ABM] and medial [MAN] nuclei [n.]), hypothalamus (dorsomedial n. [DMN] and lateral [LH]) and somatosensory cortex. In the ABL and ACN, increased maximal binding(B_max) in obese rats was associated with decreased affinity (increased K_d). Three weeks after surgery, sham-operated obese rats gained 27% more weight than lean rats but lean and obese Adx rats gained the same amount of weight. Adx reduced [³H]PRZ binding in both lean and obese rats by 37-70% in the amygdala (ABM, ACN, MAN) compared to sham-operated rats. But, Adx selectively reduced [³H]PRZ binding only in lean rats in the ABL, DMN, ventromedial hypothalamic n. (VMN) and ventroposteromedial thalamic n. In most areas, decreases in maximal binding (B_max) associated with Adx were accompanied by decreases in K_d. Unlike [³H]PRZ binding, there was no consistent genotype difference in [³H]PAC binding although Adx was followed by increased binding in obese and decreased binding in lean rats in the ABL. In only the VMN, obese rats had a 21% higher α₂- to α₁-adrenoceptor ratio than lean White widespread differences in brain α₁-adrenoceptor binding between lean and obese rats may be important, the selectively higher VMN α₂-/α₁- ratio may be critical to the pathogenesis of obesity.