Fat, carbohydrate, and the regulation of energy intake.

High-fat foods are readily overeaten. This could be because fat increases the palatability and energy density of foods or because fat has a low satiety value compared with carbohydrate. In several studies examining the effects of preloads that varied in fat and carbohydrate content on subsequent food intake, there was little difference in the effects of fat and carbohydrate on satiety. A dose-response preloading paradigm gives the most sensitive index of satiety. In one such test it was found that the effects of yogurts varying in fat or carbohydrate content did not differ in normal-weight, unrestrained men. However, in obese individuals or those concerned with body weight, fat in the yogurts was less effective in reducing subsequent food intake than carbohydrate. More studies are required to determine whether this small, but significant, insensitivity to energy from fat affects the regulation of food intake and body weight.

Amino acid imbalance, a nutritional model: serotonin3 mediation of aversive responses.

The feeding responses to essential dietary amino acid (AA) disproportion have been useful in nutritional studies. These responses involve first: recognition of the imbalance and second: rejection of the diet, likely via development of a learned aversion. In the rat, we have studied the role of the limiting AA and protein synthesis in the recognition phase by replacement of the limiting AA into a brain area essential for the initial depressed feeding response. We have also reported a reciprocal relationship between serotonin (5HT) activity and intake of imbalanced diets. High doses of the 5HT3 receptor antagonist, ICS 205-930 (ICS; 9 mg/kg IP), restored food intake to 85% or more of control intake. In the present experiments, similar treatment with ICS blocked the classical conditioned taste aversion to a saccharin solution paired with lithium chloride. These results suggest that the increased intake of AA imbalanced diets after ICS may be due to 5HT-mediated blockade of a learned aversion.

Dietary crude protein increases slightly the requirement for threonine in kittens.

Previous work indicates that the essential amino acid requirements for kittens are not positively correlated with the concentration of dietary nitrogen as they are in other species. In the studies presented here, the interaction between graded levels of threonine and dietary crude protein was investigated. Dose-response curves were generated using six 4 x 4 Latin squares. Each square represented one concentration of threonine (4.0, 5.0, 6.0, 7.0, 9.0 or 12.0 g/kg diet) and four concentrations of crude protein (150, 200, 300 and 500 g/kg diet). Food intake, weight gain, nitrogen retention and plasma amino acids were measured. There was no strong positive relationship between the threonine requirement of kittens and dietary crude protein. Increasing crude protein when threonine was limiting in the diet increased growth and food intake under some conditions, whereas under other conditions food intake and growth were decreased in a manner consistent with an amino acid imbalance response. An additional experiment was done to verify some of these findings. The requirement for threonine was found to increase from 5.0 g/kg diet at 150 and 200 g crude protein/kg diet to 6.0 g/kg diet when crude protein was 300 or 500 g/kg diet. The requirement for crude protein in the kitten appears to be between 200 and 300 g/kg diet.

Threonine is catabolized by L-threonine 3-dehydrogenase and threonine dehydratase in hepatocytes from domestic cats (Felis domestica).

Isolated hepatocytes were used to study threonine catabolism in kittens, and dietary threonine and crude protein were varied to study enzyme adaptation. Cells were isolated from 21-wk-old kittens which had been fed diets containing threonine at 4 or 8 g/kg of diet with either 200 or 500 g crude protein/kg of diet (2 x 2 factorial, n = 4/group). Production of CO2, glucose and various metabolites from [U-14C]threonine were measured. Inclusion of 10 mmol/L glycine, or glycine in combination with 10 mmol/L acetaldehyde +ethanol, in the incubation medium decreased formation of 14CO2 and [14C]glucose. At the same time, large amounts of [14C]glycine but no [14C]ethanol was formed. Inclusion of 10 mmol/L 2-ketobutyrate + 2-hydroxybutyrate decreased 14CO2 but not [14C]glucose production and resulted in the formation of [14C]2-hydroxybutyrate. Under all incubation conditions, 14CO2 and [14C]glucose production changed in response to alterations in dietary protein but not dietary threonine. It appears that threonine dehydratase and L-threonine 3-dehydrogenase, but not threonine aldolase, are active pathways for threonine metabolism in cats, and both enzymes are sensitive to levels of dietary protein.

Serotonin3 receptor antagonists block anorectic responses to amino acid imbalance.

The role of serotonin3 (5-HT3) receptors in the initial food intake depression of rats ingesting amino acid imbalanced or high-protein diets was investigated. The 5-HT antagonists metergoline, pirenpirone, ICS 205-930, and MDL 72222, the dopamine antagonist pimozide, or the alpha-adrenergic antagonist phentolamine were injected 15-45 min before presentation of test diets. Food intake was measured at intervals for 3 days. The 5-HT3 antagonists, ICS 205-930 and MDL 72222, restored feeding of a mild isoleucine (Ile)-imbalanced diet to control levels, although MDL 72222 had a longer time course of action. ICS 205-930 also increased intake of a severe Ile-imbalanced diet and Thr-imbalanced diet but not a high-protein (44% casein) diet. Treatment with metergoline, which blocks 5-HT1, 5-HT2, and dopamine receptor sites but not 5-HT3 sites, increased intake of the basal diet at 3 and 6 h but did not significantly alter intake of the mild Ile-imbalanced diet. Although pimozide tended to increase intake of the mild imbalanced diet, neither dopamine nor alpha-adrenergic receptor antagonism significantly affected imbalanced diet intake. Thus 5-HT3 receptors may mediate the anorexigenic activity of 5-HT associated with feeding an amino acid-imbalanced diet.

Adrenal hormones and the anorectic response and adaptation of rats to amino acid imbalance.

The role of adrenal function in the anorectic response and adaptation of rats to a diet with an isoleucine (Ile) imbalance was investigated. In the first of four experiments, rats were fed a mildly Ile-imbalanced diet after treatment with metyrapone, and inhibitor of glucocorticoid synthesis. In two separate experiments, rats were presented with either a mildly or severely Ile-imbalanced diet (4.93 and 9.86% imbalanced amino acid mixture, respectively) after bilateral adrenalectomy. Finally, the effects of ICS 205-930, a serotonin-3 receptor antagonist, on the intake of mildly Ile-imbalanced diet were tested in adrenalectomized animals. In each experiment a 2 X 2 factorial design was used. Neither metyrapone nor adrenalectomy altered the initial depression in the intake of an imbalanced diet. The adaptation phase in the response of adrenalectomized rats fed a mildly Ile-imbalanced diet was not different from that of controls, but adrenalectomized rats fed severely Ile-imbalanced diets were unable to adapt. Adrenalectomy did not alter the anti-anoretic activity of ICS 205-930 in this model. These results suggest that adrenal hormones are not necessary for the initial anoretic response or adaptation of rats to an Ile-imbalanced diet, nor are they implicated in the anti-anorectic effect of serotonin-3 blockade.