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Am J Physiol Endocrinol Metab 270: E677-E688, 1996;
0193-1849/96 $5.00
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AJP - Endocrinology and Metabolism, Vol 270, Issue 4 E677-E688, Copyright © 1996 by American Physiological Society

ARTICLES

Hypothalamic monoaminergic activity in obese Zucker rats in response to acute and chronic dietary stimuli

S. E. Specter, J. S. Stern and B. A. Horwitz
Department of Nutrition, School of Medicine, University of California, Davis 95616-8519, USA.

Monoamine neuromodulators link diet-related signals with autonomic responses in the regulation of energy balance. In view of evidence that sympathetically mediated expenditure is blunted in genetically obese (fa/fa) Zucker rats, a central defect in neurochemical activity has been proposed. This study tested the hypothesis that genotypic differences in monoaminergic activity in the hypothalamus underlie a blunted sensitivity of fa/fa rats to acute and chronic dietary stimuli, leading to less effective modulation of energy metabolism. Homozygous lean and obese Zucker rats were fed a protein-restricted (PR, protein = 8% of total dietary energy) or control (CF, 21% protein) diet from the age of 5 wk. At 10 wk of age, postprandial oxygen consumption (thermic effect of food, TEF) and levels of brown adipose tissue (BAT) uncoupling protein were significantly elevated (P < 0.0005) in PR vs. CF lean rats. Serotonin turnover was significantly (P < 0.0014) greater in the ventromedial hypothalamus (VMH) of meal-fed lean PR (vs. CF) rats, consistent with the suggestion that VMH serotonin release stimulates sympathetic outflow and may signal a heightened drive for protein intake. Serotonergic activity, BAT uncoupling protein, and TEF were not elevated in PR obese rats in response to a test meal, supporting the view that activation of sympathetic outflow in response to diet-related stimuli in fa/fa rats is impaired.


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