Defective glucoregulation of brain alpha 2-adrenoceptors in obesity-prone rats.
Only half the male Sprague-Dawley rats fed high-energy diets develop diet-induced obesity (DIO); the rest are diet resistant (DR). It has been established that rats prone to develop DIO have decreased basal brain alpha 2-adrenoceptor levels compared with DR-prone rats and that DIO- but not DR-prone rats show glucose-induced increases in plasma norepinephrine (NE) levels. Because it has also been shown that alpha 2-adrenoceptors modulate ingestive and autonomic functions and are responsive to changes in plasma glucose levels, we tested the hypothesis that DIO- and DR-prone rats would regulate these receptors differently by using hyperinsulinemic clamping to vary plasma glucose levels. Rats with low glucose-induced plasma NE responses (DR-prone) showed significant positive correlations (r = 0.724-0.919) between plasma glucose levels and alpha 2-adrenoceptor ([3H]paraminoclonidine) binding in 5 of 17 brain areas (anterior, ventromedial, and arcuate hypothalamic nucleus; medial and basomedial amygdalar nucleus) assessed by autoradiographic techniques. Near-significant correlations were also seen in the paraventricular nucleus and lateral hypothalamus. High glucose-induced NE responders (DIO-prone) showed such a correlation only in the arcuate nucleus (r = 0.726). There was little glucoregulation of alpha 1-adrenoceptors. The defective ability of DIO-prone rats to alter brain alpha 2-adrenoceptors to changes in plasma glucose levels might underlie their predisposition to become obese on diets high in sucrose.
Levin
B E
BE
Neurology Service, Department of Veterans Affairs Medical Center, East Orange, New Jersey 07018.
Planas
B
B
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000502:physiology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D004198:Disease Susceptibility; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000209:etiology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution
D000316:Adrenergic alpha-Agonists; D001786:Blood Glucose; D011942:Receptors, Adrenergic, alpha; C016986:apraclonidine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin