Activation of hypothalamic serotonin receptors reduced intake of dietary fat and protein but not carbohydrate.
Systemic treatment with dexfenfluramine (dF), fluoxetine, or serotonin (5-hydroxytryptamine, 5-HT) recently was shown to suppress fat and occasionally protein but not carbohydrate intake in rats when a macronutrient selection paradigm was employed. These reports contrast with the prevailing literature, which for the past decade has described a role for serotonin neurotransmission in the modification of dietary carbohydrate consumption. To test the hypothesis that the suppression of fat selection and/or consumption by systemic serotonin agonists involves stimulation of central 5-HT receptors, a series of experiments was performed in nondeprived rats. In experiment 1, third cerebroventricular (3V) infusion of the nonselective 5-HT antagonist metergoline prevented the reduction in fat but not carbohydrate feeding caused by systemic dF. Furthermore, 3V metergoline alone increased fat intake. In experiments 2 and 3, 3V infusion of 5-HT(1B/2C) receptor agonists D-norfenfluramine (DNF) or quipazine inhibited fat intake exclusively. Next, the infusion of DNF or 5-HT into the region of the paraventricular nucleus (PVN) reduced both fat and protein intake (experiments 4 and 5). Finally, in experiment 6, when rats were grouped by baseline diet preference, 5-HT infused into the PVN led to a dose-related decrease in fat intake in both carbohydrate- and fat-preferring rats. In contrast, there were no dose effects of 5-HT on carbohydrate or protein intake in either preference group. However, in fat-preferring rats, the highest dose of 5-HT reduced intake of all three macronutrient diets. These results demonstrate a selective effect of exogenous serotonergic drugs in the hypothalamus to reduce fat rather than carbohydrate intake and suggest that higher baseline fat intake enhances responsivity to serotonergic drugs.
Smith
B K
BK
Obesity, Diabetes and Metabolism Section, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA. smithbk@mhs.pbrc.edu
York
D A
DA
Bray
G A
GA
D000818:Animals; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000378:metabolism*; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000502:physiology; D015398:Signal Transduction
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D011985:Receptors, Serotonin; D012701:Serotonin