Reduced paraventricular nucleus norepinephrine responsiveness in obesity-prone rats.
Male Sprague-Dawley rats prone to develop diet-induced obesity (DIO-prone) when fed a high-energy diet have several deficits in brain noradrenergic function compared with diet-resistant (DR) rats. To further characterize these deficits, 3-mo-old rats were identified prospectively as being DIO- or DR-prone rats by their high (DIO-prone) or low (DR-prone) 24-h urine norepinephrine (NE) levels. Saturation-binding studies with 0.2-20 nM [3H] paraminoclonidine to alpha 2-adrenoceptors showed 27-54% decreases in maximal binding capacity in the anterior hypothalamic area, paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMN), and basolateral amygdalar nucleus of DIO- vs. DR-prone rats. The areal extent of the VMN was selectively reduced by 15% in DIO-prone rats. Freely moving, catheterized DIO-prone rats had higher basal plasma glucose (9%) and insulin (31%) levels. Bilateral 3 nmol NE infusions over 20 min into the PVN increased plasma NE (175%) and insulin (31%) levels in DR-prone rats but decreased plasma insulin by 17% and did not alter plasma NE levels in DIO-prone rats. PVN NE infusions had no effect on plasma epinephrine or glucose or motor activity in either group. Thus reduced PVN alpha 2-adrenoceptor binding is associated with a selective reduction in NE-induced sympathetic activation and insulin release, suggesting a postsynaptic, noradrenergic deficit in DIO-prone rats.
Levin
B E
BE
Neurology Service, Department of Veterans Affairs Medical Center, East Orange, New Jersey 07018, USA.
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism; D004032:Diet; D004198:Disease Susceptibility; D007031:Hypothalamus / Q000378:metabolism; D007267:Injections; D007328:Insulin / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology*; D009765:Obesity / Q000209:etiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D014018:Tissue Distribution
D000316:Adrenergic alpha-Agonists; D007328:Insulin; D011942:Receptors, Adrenergic, alpha; C016986:apraclonidine; D003000:Clonidine; D009638:Norepinephrine