Activation of hypothalamic serotonin receptors reduced intake of dietary fat and protein but not carbohydrate

Abstract

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-HT1B/2C receptor agonistsd-norfenfluramine (dNF) or quipazine inhibited fat intake exclusively. Next, the infusion ofdNF 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.

Association of physical activity and dietary behaviours in relation to the body mass index in a national sample of Iranian children and adolescents: CASPIAN Study

“…40 However, the lower consumption of fruit in those subjects with intermediate PA than the least active ones is not consistent with this explanation. Contrary to research in animals showing that serotonin -act t tivated by PA -may suppress protein intake, 41 in our study the frequency of protein intake was significantly higher in the most active children than in the two groups with lower PA level. The present study found that the frequency of consumption of dairy products was positively associated with increased activity in both boys and girls.…”

Effects of a High‐Fat Diet and Strain on Hypothalamic Gene Expression in Rats

“…Second, serotonin (5HT) levels are reduced in the hypothalamus of OM rats compared with S5B/Pl rats (10,11), and in vivo microdialysis studies showed higher concentrations of norepinephrine and 5HT in OM rats when fed a HF diet (11). This is particularly relevant because we have recently demonstrated the presence of a serotonergic system within the paraventricular nucleus that inhibits fat intake (12,13). Third, differential responses of food intake to galanin, neuropeptide Y (NPY), enterostatin, and ␤-casomorphin-(1-7) have been described between OM and S5B/Pl rats, whereas there is a similar inhibitory response to corticotrophin-releasing hormone (CRH) (14).…”

5-HT1B receptors modulate the feeding inhibitory effects of enterostatin

“…Among these receptors, 5-HT1B and 5-HT2C postsynaptic receptors are currently recognized as subtypes that process within-meal satiation and postmeal satiety [7]. Like enterostatin, 5-HT also preferentially suppresses the intake of fat when animals have dietary choice [3,33] but the receptor subtype responsible for this has not yet been identified. This action of 5-HT has been localized to the paraventricular nucleus [33].…”