Hypothalamic monoaminergic activity in obese Zucker rats in response to acute and chronic dietary stimuli.
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.
Specter
S E
SE
Department of Nutrition, School of Medicine, University of California, Davis 95616-8519, USA.
Stern
J S
JS
Horwitz
B A
BA
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D002364:Caseins / Q000494:pharmacology; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage; D005838:Genotype; D006706:Homeostasis; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption; D051381:Rats; D011924:Rats, Zucker; D012016:Reference Values; D013997:Time Factors
D015306:Biogenic Monoamines; D002364:Caseins; D004044:Dietary Proteins