Cingulate lesions and behavioral adaptation to amino acid imbalanced diets

The effect of anterior cingulate cortex lesions on dietary intake and adaptation of disproportionate amounts of amino acids was examined. Rats with bilateral electrolytic lesions in the anterior cingulate cortex and sham-operated rats were fed, in turn, amino acid basal, imbalanced or devoid diets involving threonine and isoleucine as the growth limiting amino acids, and then a low protein (6% casein) followed by a high protein (75% casein) diet. Lesions of the anterior cingulate cortex did not prevent the initial depression in food intake of the amino acid imbalanced diets, but shortened the duration of anorexia associated with dietary amino acid imbalances. Cingulate lesions did not influence the food intake of rats fed amino acid devoid diets. When switched from a low protein to a high protein diet, animals bearing lesions and sham-operated controls reduced markedly their initial food intake and adapted to the high protein diet in similar manner. It was concluded that the initial food intake depression associated with a dietary amino acid imbalance is a direct response to postingestive cues which influence food intake. Moreover, that the difference in adaptive intakes of the cingulate cortex lesioned animals who ingested a diet of imbalanced amino acids or of high protein, indicates that separate mechanisms act to control food intake of animals fed diets containing imbalanced amino acid mixtures or diets with excessive amounts of protein.     

Threonine-imbalanced diet alters first-meal microstructure in rats

Diets limiting in an essential amino acid have long been known to suppress food intake. The purpose of this study was to examine the microstructure of feeding behavior of rats within the very first meal of an imbalanced diet. Rats were preconditioned for 12 days on a Baseline diet and were then given a test diet with either a corrected amino acid profile or a diet imbalanced with respect to the essential amino acid threonine. Overall, first-meal intake and first-meal duration were robustly and significantly reduced by the Imbalanced diet but not altered by the Corrected diet. The Corrected diet caused an increase in the number of feeding bouts during the first meal. The Imbalanced diet increased the duration of pauses during the first meal. Most rats in the Imbalanced group stopped eating after just 15 min of exposure to the diet, but those still eating after this time tended to have a lower rate of eating compared to those eating the Corrected diet. On the basis of these results, we conclude that changes in microstructure and meal duration contribute to the reduction in food intake upon exposure to amino-acid-deficient diets.     

Effect of amygdaloid lesions on dietary intake of disproportionate amounts of amino acids

Male rats with bilateral electrolytic lesions in the anterior, medial or posterior aspects of the ventral amygdala and groups of intact rats were fed, in turn, basal, imbalanced or deficient amino acid diets involving threonine or isoleucine as the limiting amino acid, and then a low protein (6% casein) followed by a high protein (75% casein) diet. No change in food intake was observed in animals fed the threonine basal diet postoperatively. When the threonine or isoleucine imbalanced diet was substituted for the respective basal diet, animals with lesions in certain areas of the medial amygdala showed little or no depression in food intake of the imbalanced diets, while all other rats with amygdala lesions reduced their food intake markedly, as did intact controls, when fed such diets. All animals, however, curtailed their food intake of the deficient or high protein diets. The lack of responsiveness of the animals with medial amygdaloid lesions to the imbalanced diets suggests that these areas may be involved in a system regulating food intake of animals fed diets containing imbalanced amino acid mixtures.     

Dietary amino acid imbalance and neurochemical changes in three hypothalamic areas

The impact of feeding imbalanced amino acid diets on monoamine, metabolite and amino acid concentrations was measured in the ventromedial hypothalamus (VMH), lateral hypothalamus (LH) and paraventricular nucleus (PVN). After rats were fed either an isoleucine imbalanced diet, a threonine imbalanced diet, or the appropriate basal or corrected control diets, regional differences were found in neurochemical concentrations. Contrary to our expectations, the limiting amino acid was unchanged in the imbalanced groups, tending to be decreased only in the isoleucine imbalanced-diet group in the PVN. This is the first report that the limiting amino acid was not reduced uniformly in the brain after imbalanced amino acid feeding. In the VMH, norepinephrine (NE) was increased by 22% and 63% in the threonine and isoleucine imbalanced-diet groups, respectively. Since the concentration of NE was affected even before the decrease in feeding, both in the VMH, and, as previously reported, in the prepyriform cortex, the NE system may be involved in very early responses to imbalanced amino acid diets.     

Influence of taste on dietary choice of rats fed amino acid imbalanced or deficient diets

Diets with added quinine as the negative taste cue or saccharin as the positive taste cue were employed to determine the influence of taste on dietary choice of rats offered diets containing different proportions of amino acids (amino acid imbalance) and which differed in acceptability. The quinine was added to the protein-free or the corrected (corrected for amino acid imbalance) diet that animals normally preferred and the saccharine was added to the amino acid imbalanced or deficient diets that animals normally avoided. There appeared to be a balance in acceptance of a diet between the undesirability of the quinine and the degree of metabolic benefit from the diets with favorable metabolic or nutritional characteristics. Although the presence of higher levels of quinine could interfere with the normal dietary preference based on metabolic consequences, the animals invariably selected the metabolically favorable diet if they were forced to experience the metabolic characteristics of the diets by having to consume them exclusively. The presence of the taste cues appeared to enhance the acceptance or avoidance of diets in the choice regimens, possibly by aiding in their identification, especially to animals previously not exposed to the taste cues.     

Effects of hippocampal lesions on adaptive intake of diets with disproportionate amounts of amino acids

Bilateral double electrolytic overlapping lesions were placed in dorsal-lateral hippocampus of male 230 g rats, and their food intake responses to the ingestion of diets containing disproportionate amounts of amino acids were examined. Rats with such lesions and intact control rats maintained their normal intakes of the 6% casein basal diet or a threonine basal amino acid diet postoperatively. However, they exhibited marked initial food intake depression, similar to that of intact rats, when fed the threonine imbalanced amino acid diet. Also, animals with lesions in certain areas of the dorsal-lateral hippocampus showed facilitated adaptation to the amino acid imbalanced diet. Similar severe reduction in food intake with relative lack of adaptation were observed in both the intact controls and rats with hippocampal lesions when fed amino acid diets completely devoid of threonine. Initial food intake of rats with hippocampal lesions was inhibited drastically as was the case with the intact controls when fed a 75% casein high protein diet. All rats, either intact or lesioned, showed similar slow adaptation patterns with the prolonged ingestion of the high protein diet. The initial food intake responses and facilitated adaptation of the animals bearing lesions in certain areas of the hippocampus suggest that such areas are not crucially involved in the inhibition of food intake of rats fed disproportionate amounts of dietary amino acids. Rather, such areas of lesions in the hippocampus may play a role in a system governing the behavioral adaptation of the intake of amino acid imbalanced diets but not of diets containing amino acids in general excess. This would also indicate that different mechanisms control the intake of amino acid imbalanced diets and diets containing amino acids in excess.     

Effect of food deprivation and maintenance diet composition on fat preference and acceptance in rats

High-fat diets typically elicit greater kcal intake and/or weight gain than low-fat diets. Palatability, caloric density, and the unique postingestive effects of fat have each been shown to contribute to high-fat diet hyperphagia. Because long-term intake reflects the sum of many individual eating episodes (meals), it is important to investigate factors that may modulate fat intake at a meal. The present studies used high-fat (hi-fat) and high-carbohydrate (hi-carb) liquid diets (both 2.3 kcal/mL) to assess the effect of hunger level (0 versus 24-h food deprivation) and fat content of the maintenance diet (12 versus 48%) on fat preference (when a choice among foods is offered in a two-bottle test), and acceptance (only one food offered) in male rats. Preference for hi-fat relative to hi-carb (two-bottle test) was enhanced by 24-h food deprivation, and by a high-fat maintenance diet. In contrast, neither deprivation nor maintenance diet composition influenced relative meal size (one-bottle test) of hi-fat and hi-carb: irrespective of test conditions, meal size of hi-fat was bigger than meal size of hi-carb.     

Effects of dietary nutrients and foraging costs on meal patterns of rats

Rats were fed either a cereal-based or a purified casein-based diet in a foraging paradigm in which the costs of procurement and consumption were varied. The group offered the cereal-based diet consumed about 10% more calories than the group offered the casein-based diet, but both groups grew at the same rate. The intake of a control group offered a choice between the two diets was approximately 80% from the casein diet, and the growth of this group did not differ from that of the experimental groups. Variations in the cost of procurement and the cost of consumption affected the patterning of meals differentially for the two diets: changes in meal patterns tended to control the time and/or energy spent feeding. These results show that (1) meal patterns in the foraging paradigm are sensitive to subtle differences in diets, and (2) the amount of diet consumed (acceptance) and the choice between diets (preference) are determined by the economics of feeding and the nutritive quality of the foods, as well as by their palatability.     

Energetics of meal patterns in rats

Meal patterns in rats were examined as functions of the caloric density and availability of the diet. Three diets were used, a standard laboratory diet (3.6 kcal/g), a calorically diluted diet (2.7 kcal/g), and a calorically concentrated diet (4.5 kcal/g). After obtaining ad lib measures of meal patterns on each diet availability of food was constrained by requiring the rats to complete fixed ratio requirements of barpresses to obtain access to a meal. On all 3 diets, meal frequency decreased, while meal size and duration increased as functions of the ratio requirement. Under ad lib conditions and low ratio requirements, in comparison to the standard diet, meal frequency was greater on the diluted diet and less on the concentrated diet. Meal size did not vary as a function of diet on low ratio schedules. At high ratio requirements, rats continued to maintain caloric intake on the diluted diet by increasing meal frequency. On the concentrated diet, however, rats maintained intake at high ratio values by decreasing meal size rather than meal frequency. The results indicate that the rat can adopt a variety of strategies to solve the problem of controlling energy intake constant across the daily feeding cycle.     

Dietary selection for lysine by the chick

Broiler chicks were provided choices of synthetic diets (a) adequate or low in lysine, and (b) adequate in or devoid of lysine. In each case, chicks consumed some of each diet offered, but preference was shown for the adequate lysine diet. Growth rates of chicks given choices ranged from 80% of that of chicks fed an adequate lysine diet with no choice for two weeks, then growth rates fell to about 60% of those fed adequate lysine. In another study, chicks were fed a diet devoid of lysine but were offered pure L-lysine HCl in a separate feeder. These chicks selected some of the supplementary lysine, but their body weights were only 68% of the body weight of chicks fed an adequate lysine diet after 21 days. Chicks given a choice of diets prepared with an adequate quantity of either L- or D-lysine preferred with L-lysine diet but did not select sufficient quantity to reach normal growth. These observations indicate that chicks can discern the presence of L-lysine in diets or separately, but will not select sufficient quantity for maximum growth potential. A diet prepared with D-lysine was more acceptable than one completely devoid of lysine, suggesting some sensory recognition for lysine.     

The relation of feeding and activity following septal lesions in rats

The patterns of intake of liquid diet and water were recorded in diet-deprived rats with septal lesions and neurologically intact controls during the first hour of diet access. The occurrences of grooming, resting/sleeping, and exploring were also recorded. Both groups of rats consumed similar amounts of diet in one meal during the 1-hr diet access period. Control rats consumed the meal in one prolonged bout of eating, whereas rats with septal lesions consumed the meal in numerous small bouts of eating. Rats with septal lesions were active for longer periods, exhibiting continuous alternation of brief bouts of eating, drinking, exploring, and resting throughout the meal. In tests in which water was not available during the diet access period, both groups of rats increased their intrameal bout size, but rats with septal lesions still showed much smaller bouts of ingestion than did controls. These data suggest that the small-bout pattern of ingestion may reflect a general disruption in the control of behavioral sequences, rather than processes uniquely related to the regulation of eating or drinking.     

Palatability and meal patterns

Investigations of palatability have often been confounded by nutritional, pharmacological or methodological problems. The present experiment examined the free-feeding meal patterns of two differentially preferred yet nutritionally equivalent diets. When the two diets were offered sequentially (Experiment 1), no differences were found in meal frequency, meal size, or meal duration. However, when the diets were offered simultaneously in Experiment 2, the preferred diet was consumed more frequently, in larger meals, and at a faster feeding rate than the less preferred diet. Further, the meal patterns in Experiment 2 of the preferred diet were identical with those found for both diets in Experiment 1. Therefore, the meal patterns of two diets with differing palatability depend upon the method of presentation with differences appearing when the diets are offered simultaneously but not when they are offered sequentially.     

The paradox of satiation

Animals behave in bouts, and the process that causes feeding bouts to end is called satiation. Bout size or, in the case of feeding, meal size is the result both of the costs of food resources and the consequences of consuming a particular resource. Meal size increases as a function of increasing resource access cost; in this way, meal size is part of a strategy that economizes on time and energy spent acquiring food resources, thereby making time and effort available for competing activities. Meal size also varies as a function of the amount of the resource consumed and the animal's requirements for that resource. The paradox of satiation is that it is both a tool for economizing and a consequence of feeding.     

Effects of dietary caloric density on feeding behavior in Mongolian gerbils (Meriones unguiculatus)

Total daily energy intake, water intake, body weight, and meal patterns were studied in Mongolian gerbils as a function of dietary caloric density. On diets ranging in caloric density from 2.25 kcal/g to 6.09 kcal/g, gerbils consumed an average of 40 kcal per 100 g of body weight per day. In comparison to gerbils fed ground Purina Laboratory Chow (4.2 kcal/g), gerbils presented with diets diluted with nonutritive cellulose increased food intake in proportion to the percentage of cellulose added. Gerbils given diets in which the caloric density was increased by the addition of fat, decreased food intake as a direct function of the added fat. Water intake was increased on the calorically diluted diets, and decreased on the concentrated diets. Body weight did not vary as a function of dietary conditions. On a standard pelleted diet (Noyes), gerbils ate approximately 18 meals a day. Average meal size was 0.4 g. When presented with calorically diluted pellets, gerbils maintained daily energy intake by increasing both meal frequency and meal size. There were no differences in food intake, meal frequency or meal size between the light and dark portions of the 24-hr cycle.     

Differential Circadian Eating Patterns in Two Psychogenetically Selected Strains of Rats Fed Low-, Medium-, and High-Fat Diets

Spontaneous eating patterns in male, inbred Roman high- and low-avoidance rats (RHA/Verh, RLA/Verh) were continuously recorded while animals were successively offered three isocaloric (16.5-kJ/g) diets: a low-fat, high-carbohydrate diet (LF; 3.3% fat), a medium-fat diet (MF; 18% fat), and a high-fat diet (HF; 40% fat), the latter being followed once again by the LF diet. Under the conditions of this experiment, overall 24h food intake did not differ significantly between RHA/Verh and RLA/Verh rats, but was significantly higher for both rat strains on the MF and HF diets than on the LF diet. Despite the similar 24h-food intake, RHA/Verh rats ate transiently less than RLA/Verh rats during the third quarter of the dark phase under all dietary conditions. These differences were due to the RHA/Verh rats' longer intermeal intervals (with all diets) and smaller meals (with the MF and HF diets) and were compensated for during the last 3 h of the dark phase. On the LF diet, dark-phase meal frequency was higher and both nocturnal meal size and mean eating rate within meals were lower in RLA/Verh rats than in RHA/Verh rats. With the MF and HF diets, mean nocturnal meal size and meal duration were higher and mean eating rate was lower in RLA/Verh rats than in RHA/Verh rats. For both strains, nocturnal meal size was significantly higher with the MF and HF diets than with the LF diet, and nocturnal meal frequency was lower with the HF diet than with the other two diets. Although body weights were similar at the start of the study, RLA/Verh rats gained significantly more weight than did RHA/Verh rats by the end. As has often been the case with other aspects of behavior studied, differences in neuromodulatory systems (e.g., serotoninergic and dopaminergic) between RHA/Verh and RLA/Verh rats may directly or indirectly contribute to the subtle differences in eating patterns observed here.     

Norepinephrine and amino acids in prepyriform cortex of rats fed imbalanced amino acid diets

Monoamines and amino acids were measured in anterior prepyriform cortex (PPC) and anterior cingulate cortex (CC) of male Sprague-Dawley rats after they were offered basal, imbalanced (IMB) or corrected amino acid diets, limited in threonine (THR) or isoleucine (ILE). In the THR study, brains were taken after 2.5 hr of feeding, when intake of THR-IMB was just depressed. In the ILE study the brains were taken after 3.5 hr on ILE-IMB, a less severely imbalanced ration, before the onset of food intake depression. The PPC has been shown to be involved in the acute response of animals to imbalanced amino acid diets. In the PPC from the IMB diet groups, NE was reduced by 30%, but the other monoamines were unchanged. In CC, an area involved in the adaptive, but not the acute feeding response to imbalanced diets, the monoamines were unchanged in the IMB diet groups. In both studies, in both tissues, the limiting amino acids were decreased in the IMB groups, although the decrease of ILE in the CC failed to reach significance. The remaining indispensable amino acids, added to create the imbalance, were slightly reduced in the THR-IMB group, but not in the ILE-IMB group in both tissues. Thus, the amino acid patterns were altered in the PPC and CC, as they are in whole brains from animals fed imbalanced amino acid diets. These results also suggest that the concentration of NE in the PPC may be associated with the initial food intake response of animals to imbalanced amino acid diets.     

High-fat diet preference in developing and adult rats

Diet preference tests in rats have yielded equivocal results, as some investigators have reported a strong preference for diets high in fat over those containing less fat, while others have failed to see this preference. To further explore this unresolved problem, two diet preference experiments were conducted. In Experiment 1, adult rats were maintained for at least three months on one of three powdered diets (control, high-carbohydrate or high-fat). Rats were then given a preference test with all three diets available. Animals from each group overwhelmingly preferred the high-fat diet. To determine whether this preference was also present in younger, developing rats, in Experiment 2, weanling animals were tested with the same three diets as in Experiment 1. As observed with adult animals, weanling rats also showed a strong preference for the high-fat diet. The idea that rats prefer a diet with a relatively high level of fat is supported. Possible explanations for these findings are discussed.     

Independent effects of diet palatability and fat content on bout size and daily intake in rats

Although considerable evidence attests to the hyperphagic effects of high-fat (HF) diets, the attribute(s) of these diets (e.g., palatability, caloric density, and postingestive effects) which promote overeating is still unclear. The present studies investigated the independent effects of diet palatability and macronutrient composition on intake using the self-regulated intragastric infusion paradigm. In Experiment 1, rats were infused with either HF or high-carbohydrate (HC) diet while drinking either saccharin (Sacc) or a more palatable saccharin-glucose (SaccGlu) test solution for 9 days. HF elicited greater daily intake than HC; lick pattern analysis revealed that HF produced larger but not more frequent bouts. Test solution was not related to intake, possibly due to the relatively modest palatability manipulation. Experiment 2 provided a more sensitive test: The palatability manipulation was strengthened and diet infusion made optional by provision of chow. HF again elicited larger bout size and total daily intake (diet+chow) than HC. Rats given the more palatable solution significantly increased intake (via larger bouts) and thus the amount of diet infused, but chow intake decreased such that total kilocalorie intake was not significantly related to solution palatability. The reliable observation that HF promoted larger bout size and greater total kilocalorie intake than HC provides additional evidence that fat sends weaker feedback signals relevant to controls of both satiation (suppression of ongoing eating, behaviorally manifest in meal size) and satiety (suppression of subsequent intake, reflected in total daily intake).     

Acute exposure to a high-fat diet alters meal patterns and body composition

Weight gain and adiposity are often attributed to the overconsumption of unbalanced, high-fat diets however, the pattern of consumption can also contribute to associated body weight and compositional changes. The present study explored the rapid alterations in meal patterns of normal-weight rats given continuous access to high-fat diet and examined body weight and composition changes compared to chow fed controls. Ten Long-Evans rats were implanted with subcutaneous microchips for meal pattern analysis. Animals were body weight matched and separated into two groups: high-fat or chow fed. Each group was maintained on their assigned diet for nine days and monitored for 22 h each day for meal pattern behavior. Body weight was evaluated every other day, and body composition measures were taken prior and following diet exposure. High-fat fed animals gained more weight and adipose tissue than chow fed controls and displayed a reduced meal frequency and increased meal size. Furthermore, meal size was significantly correlated with the gain of adipose tissue. Together, these results suggest that consumption of a high-fat diet can rapidly alter meal patterns, which in turn contribute to the development of adiposity.     

Acquisition of dietary self-selection in rats with normal and impaired oral sensation

To study the mechanisms of dietary self-selection, the dietary choice behavior of rats was observed for up to 5 weeks, beginning on the first day of exposure to two nutritionally different diets, a high-protein diet (44% protein) and a protein-free carbohydrate diet. In Experiment 1 normal rats selected equal amounts of the two selection diets at first and over a 7-day period gradually modified the choice ratio until a stable protein intake of 14.6% (SE,0.4) of total intake was reached. In Experiment 2 rats were subjected to partial trigeminal deafferentation, which impairs oral somatosensory input (touch, temperature, pain), before the two selection diets were introduced. The deafferented animals did not develop a stable selection pattern; their protein ratio varied over the entire possible range (0-44%) throughout the experiment. It is hypothesized that quantitative protein/carbohydrate selection involves an associative learning process in which somatosensory inputs from the feeding activity and/or from the properties of the food link dietary choice behavior to later metabolic consequences.