A role for sweet taste: calorie predictive relations in energy regulation by rats

Animals may use sweet taste to predict the caloric contents of food. Eating sweet noncaloric substances may degrade this predictive relationship, leading to positive energy balance through increased food intake and/or diminished energy expenditure. These experiments were designed to test the hypothesis that experiences that reduce the validity of sweet taste as a predictor of the caloric or nutritive consequences of eating may contribute to deficits in the regulation of energy by reducing the ability of sweet-tasting foods that contain calories to evoke physiological responses that underlie tight regulation. Adult male Sprague-Dawley rats were given differential experience with a sweet taste that either predicted increased caloric content (glucose) or did not predict increased calories (saccharin). We found that reducing the correlation between sweet taste and the caloric content of foods using artificial sweeteners in rats resulted in increased caloric intake, increased body weight, and increased adiposity, as well as diminished caloric compensation and blunted thermic responses to sweet-tasting diets. These results suggest that consumption of products containing artificial sweeteners may lead to increased body weight and obesity by interfering with fundamental homeostatic, physiological processes.     

Caloric regulation and patterns of food choice in a patchy environment: the value and cost of alternative foods

Rats in a laboratory foraging paradigm had 24-hr-per-day access to a feeder where they could search, by completing a fixed number of bar presses, for an opportunity to eat one of a pair of foods differing in caloric density (2.5, 3, 3.5, or 4 kcal/g) and, in Experiment 2, the price of food pellets (10 to 50 bar presses per pellet). The rats could either accept the opportunity, and eat a meal, or reject it in favor of further search. Daily caloric intake was relatively constant. The rats always included both foods in their diet, but, for any particular food, the degree of inclusion in the diet and of acceptance of meal opportunities, the meal size, and the rate of eating were all functions not only of the price and caloric value of that food but also of the price and value of the alternately-available food. The patterns of intake for one food relative to those for the other available food were strongly correlated with the relative rate of calorie intake during consumption of that food compared to the other. Although the rats appeared to be sensitive to the local rates of calorie flow, they did not maximize daily calories consumed per time spent feeding.     

Consumption of salty food by rats: regulation of sodium intake?

The extent to which sodium levels may be regulated by consumption was examined in two experiments that offered rats foods varying in sodium chloride (NaCl) content. In the first, rats received single purified diets containing from 0% to 3% NaCl. There were no effects of NaCl level on the amount or pattern of daily food intake; water intake, however, increased with salt content. In the second study, rats had choices between a NaCl-free food and a food containing either 1, 2, or 3% NaCl for 1 week each. Total food intake was unaffected. Proportional intake of the salt-free option increased with the salt content of the alternate food, but not sufficiently to maintain a constant NaCl intake. After 8 weeks of exposure to a single food, intake of the salty option increased in the choice tests, but the level of NaCl (from 0.5 to 3.0%) in the exposure-phase food did not affect the subsequent choice. We conclude that when only one food is available, salt intake is governed by caloric requirements and sodium levels are regulated by excretion. When foods differing in NaCl content are available, consumption does contribute to the regulation of sodium balance, but the amount consumed is not tightly controlled. Rats' salt preference appears to increase with age or with experience eating the purified foods offered here, but experience eating salty food does not affect the preferred level of salt.     

Changes in rats' meal patterns as a function of the caloric density of the diet

Rats in a laboratory foraging paradigm were offered each of four diets which differed in caloric density, and intakes, meal frequencies, meal sizes, and eating rates were monitored. The rats maintained a constant daily caloric intake by eating more frequent, larger meals of the lower density foods. However, caloric meal size was not regulated, and significant correlations between meal size and the length of the post-meal interval were rarely found. The 24-hour pattern of calorie intake was the same regardless of diet. Higher-calorie foods were consumed at a faster rate within meals than were lower-calorie foods. The feeding patterns observed suggest that caloric intake may be regulated over a time frame of several meals rather than on a meal-to-meal basis.     

Caloric compensation in rats with combined lesions in lateral and ventromedial hypothalamus

Compensatory adjustment of caloric intake in response to stomach loading of glucose or vegetable oil was studied in rats with lateral hypothalamic (LH) or with combined lateral and ventromedial hypothalamic (VMH) lesions. The LH lesioned rats as well as the sham operated controls compensated the loaded calories by an adequate reduction of oral intake, but those bearing both LH and VMH lesions tended to undercompensate with increased total caloric intake and body weight during some but not all periods of loading. Some of the rats with combined LH and VMH lesions displayed characteristics of the respective syndrome, such as thirst deficit and hyperphagia.     

Increased sucrose intake and corresponding c-Fos in amygdala and parabrachial nucleus of dietary obese rats

The intake-excitatory effects of caloric foods are mainly due to the palatable taste and the ensuing positive postingestive effects. Dietary obese individuals are inclined to overeat high caloric foods. However, it is still unclear whether the taste or postingestive reinforcement mainly contributes to the excessive intake by obese individuals. In the present study, we measured 10- or 120-min sucrose solution drunk by dietary obese rats and measured c-Fos expression following 120-min tests in the central nucleus of amygdala (CeA), a forebrain nucleus involved in the hedonic reward and craving, and the parabrachial nucleus (PBN), a taste relay area responsive to positive postingestive effects. Dietary obese rats, compared with those fed normal chow, ingested larger amounts of sucrose solution (0.25 M) in the 120-min test, but not in the 10-min test. In addition, significantly more sucrose-induced c-Fos positive cells were found in the CeA, but much less in the external lateral subnucleus of the PBN of dietary obese rats. Our results demonstrate that increased sucrose intake in dietary obese rats is mainly due to the alteration of postingestive effects. The differences in these postingestive effects in obesity may involve greater positive/excitatory signals in which the CeA may play a role, and less negative/inhibitory signals in which the el-PBN may be involved.     

The nature of the metabolic signal that triggers onset of puberty in female rats

These experiments examined the effects of different refeeding stimuli on reproductive activity as measured by the onset of first estrus in prepubertal, food-restricted female rats. Such rats were placed on a restricted food intake until day 50 of age to maintain a weight of 80-90 g, and to suppress onset of puberty (normal time of puberty: 37 +/- 1.4 days of age). In Experiment 1, rats were refed at different daily caloric intakes from day 50 through day 62. First estrus was observed in all rats, with highest caloric intake after 5.7 +/- 0.6 days of refeeding. Progressively fewer rats achieved first estrus, and the time to first estrus increased as the caloric intake per day decreased. These results suggest that the highest caloric intake most closely resembles an ad lib diet in such realimented rats. The second experiment determined the duration of an ad lib food stimulus needed to initiate first estrus. Similarly growth-restricted rats were refed (on Day 50 of age) ad lib meals of 67.2 +/- 0.1 kcal, presented for periods of 12, 24, 48, or 72 h. The majority of rats (6 of 7) achieved first estrus when the ad lib meals were presented for 72 h, but progressively fewer rats achieved first estrus when such meals were presented for less time. These data indicate that an extended ad lib food stimulus (72 h) is necessary to cause onset of cycling in the majority of food-restricted, prepubertal female rats.     

Responses to protein dilution in the adult female rat

Adult female rats were given ad lib access to 3 food cups containing casein, cornstarch, and a fat mixture, or a composite diet formulated from these nutrients. One-half of the animals in each diet condition were subjected to 25, 50, 150, and 500% sequential dilutions of the casein or the composite diet. Self-selecting rats decreased intake of the diluted casein, but increased consumption of cornstarch, so that total caloric intake remained constant. Composite-fed rats compensated for dilution by increasing the volume of diet consumed, but caloric regulation was less precise than in self-selectors.     

Flavor-cued modulation of intake in rats: role of familiarity and impact on 24-h intake.

Following training with distinctively flavored nutritive solutions that differ in concentration and thus in caloric value, rats demonstrate flavor-postingestive consequence learning by preferentially consuming one of the flavors in two-bottle tests (both flavors in nutrient-identical solutions.) Experiment 1 investigated whether the relative familiarity of the flavor-nutrient combinations encountered in two-bottle tests contributes to the observed preference. One of the training concentrations (rather than the customary intermediate concentration) was used to present the flavors in testing; thus, one of the flavors was in a familiar context while the other was in an unfamiliar context. The results of two independent trials (rats trained with 1 and 5% sucrose; rats trained with 5 and 40% sucrose) confirmed that two-bottle test preference was not a preference for the familiar flavor-nutrient combination. Experiment 2 examined whether caloric expectancies based upon a previously learned flavor-postingestive consequence association would affect total daily intake. On alternating days, rats consumed 30 mL of dilute (5%) and concentrated (40%) sucrose, each distinctively flavored. When given 30 mL of 22.5% sucrose containing each of the flavors on separate test days, they ate less chow and thus fewer total calories over 24 h when given the flavor previously paired with concentrated sucrose. Experiment 3 replicated the design of Experiment 2 except that fat calories were used instead of sucrose; no significant adjustment of chow intake in extinction tests was noted, even when the number of fat calories used in training was increased (Experiment 4). Thus, rats did not exhibit flavor-cued modulation of chow intake when trained with fat, in contrast to responsivity to flavor cues when trained with sucrose. This differential responding to fat versus carbohydrate calories is consistent with previous observations, in a variety of paradigms, that modulation of caloric intake is less energetically appropriate when ingested foods are high in fat relative to high-carbohydrate foods.     

Self-selection and the obese Zucker rat: the effect of dietary fat dilution

Adult female lean and obese Zucker rats were allowed to compose their own diets by giving them access to three macronutrient sources. After a baseline period, the fat source was serially diluted. In all, eight concentrations of fat were used. Dilution of the fat source promoted significant increases in the intake of fat by both lean and obese rats. The increased intake of fat was not simply compensatory in nature, but rather represented significant increases in fat consumption. These results suggest that the reported increased appetite for fat of the obese rat is not a unique trait of that genotype. Further, results from this experiment demonstrate that caloric and protein regulation mechanisms may not be controlling the intake of obese and lean rats as precisely as once believed.     

Children's food intake following drinks sweetened with sucrose or aspartame: time course effects

In two experiments, 2-5-year-old children's responsiveness to caloric density cues was examined. In a preloading protocol, consumption of fixed volumes of drinks (205 ml in Experiment 1; 150 ml in Experiment 2), sweetened with sucrose, aspartame, aspartame plus low glucose maltodextrin, or a water control, was followed by ad lib consumption from among a variety of foods. Caloric drinks had about 90 kcal in Experiment 1, 65 kcal in Experiment 2. The delay interval between the preload and the ad lib consumption was 0, 30 or 60 minutes. In Experiment 1, 24 4- and 5-year-old children participated in only one delay interval, while in Experiment 2, all 20 2- and 3-year-old children were seen in all conditions. Results revealed evidence of caloric compensation, but no evidence of preload x time delay interaction. In both experiments, aspartame also produced a significant suppression of intake relative to water, primarily due to the pattern at 30 min following the preload. Across conditions, the suppression following aspartame was usually significantly less than that produced by the caloric sweet drinks, providing evidence for postingestive effects. In Experiment 1, suppression of intake was related to the children's preferences for the foods, not to macronutrient content; consumption of nonpreferred foods was most suppressed. Consumption of sweetened drinks as long as 1 hour prior to eating suppressed food intake, and this common feeding practice may also reduce dietary variety.     

Effects of CB(1) and CRF(1) receptor antagonists on binge-like eating in rats with limited access to a sweet fat diet: Lack of withdrawal-like responses

Positive reinforcement (e.g., appetitive, rewarding properties) has often been hypothesized to maintain excessive intake of palatable foods. Recently, rats receiving intermittent access to high sucrose diets showed binge-like intake with withdrawal-like signs upon cessation of access, suggesting negative reinforcement mechanisms contribute as well. Whether intermittent access to high fat diets also produces withdrawal-like syndromes is controversial. The present study therefore tested the hypothesis that binge-like eating and withdrawal-like anxiety would arise in a novel model of binge eating based on daily 10-min access to a sweet fat diet (35% fat kcal, 31% sucrose kcal). Within 2-3weeks, female Wistar rats developed binge-like intake comparable to levels seen previously for high sucrose diets (~40% of daily caloric intake within 10min) plus excess weight gain and adiposity, but absent increased anxiety-like behavior during elevated plus-maze or defensive withdrawal tests after diet withdrawal. Binge-like intake was unaffected by pretreatment with the corticotropin-releasing factor type 1 (CRF(1)) receptor antagonist R121919, and corticosterone responses to restraint stress did not differ between sweet-fat binge rats and chow-fed controls. In contrast, pretreatment with the cannabinoid type 1 (CB(1)) receptor antagonist SR147778 dose-dependently reduced binge-like intake, albeit less effectively than in ad lib chow or sweet fat controls. A priming dose of the sweet fat diet did not precipitate increased anxiety-like behavior, but rather increased plus-maze locomotor activity. The results suggest that CB(1)-dependent positive reinforcement rather than CRF(1)-dependent negative reinforcement mechanisms predominantly maintain excessive intake in this limited access model of sweet-fat diet binges.     

Caloric regulation in the rat: control by two factors

These experiments demonstrate that rats can immediately adjust their meal size in response to variations in the caloric density of a novel diet. However, this immediate caloric sensitivity only seems to appear when rats have been adapted to small, calorically insufficient meals. Rats in Experiment 1 were given timed access to unlimited quantities of an oil/water diet during baseline, and they showed no indication of compensating for changes in the caloric density of the oil/water diet during a test meal. Instead, they consumed about the same amount they had consumed during the preceding baseline meal, suggesting that a learned habit of consuming a certain volume of food controlled their meal size. In contrast, rats that were accustomed to receiving only a very small quantity of food for one of their daily meals during baseline immediately responded to the caloric density of an oil/water test diet by consuming a larger meal if the diet was dilute than if it was calorically more concentrated (Experiments 2 and 3). This immediate sensitivity to caloric density occurred whether or not the rats were exposed to the oil/water diet during baseline, suggesting that rats have some way of directly "metering" the caloric density of new foods. Thus, rats' caloric intake during a meal appears to be controlled by two factors: under certain conditions, control is by caloric learning, under other conditions control is by a caloric metering mechanism.     

Changes in macronutrient selection as a function of dietary tryptophan

It has been hypothesized that the serotonergic system is involved in the regulation of carbohydrate and/or protein intake. Tests of this hypothesis using added dietary tryptophan and diets varying in the ratio of carbohydrate/protein resulted in depressed intakes of high carbohydrate/low protein diets, elevated intakes of low carbohydrate/high protein diets, and a reduction of total caloric intake. The present studies gave rats increased options for adjusting to added tryptophan by providing them with separate sources of protein, carbohydrate, and fat. The results showed the expected decrease in carbohydrate intake, but also increases in fat intake and, to a lesser extent, protein intake. Total caloric intake was conserved. Hypothalamic concentrations of serotonin and 5-hydroxyindole acetic acid indicated increased activity of the serotonergic system. These results lend support to serotonin's involvement in nutrient selection, in that carbohydrate consumption decreased in response to tryptophan loading, but indicate that other nutrients may also be affected. Given the option of altering fat intake, the animals maintained a constant caloric intake despite the reduction of carbohydrate consumption.     

Fat substitutes promote weight gain in rats consuming high-fat diets

The use of food products designed to mimic the sensory properties of sweet and fat while providing fewer calories has been promoted as a method for reducing food intake and body weight. However, such products may interfere with a learned relationship between the sensory properties of food and the caloric consequences of consuming those foods. In the present experiment, we examined whether use of the fat substitute, olestra, affect energy balance by comparing the effects of consuming high-fat, high-calorie potato chips to the effects of consuming potato chips that sometimes signaled high calories (using high-fat potato chips) and that sometimes signaled lower calories (using nonfat potato chips manufactured with the fat substitute olestra). Food intake, body weight gain and adiposity were greater for rats that consumed both the high-calorie chips and the low-calorie chips with olestra compared to rats that consumed consuming only the high-calorie chips, but only if animals were also consuming a chow diet that was high in fat and calories. However, rats previously exposed to both the high- and low-calorie chips exhibited increased body weight gain, food intake and adiposity when they were subsequently provided with a high fat, high calorie chow diet suggesting that experience with the chips containing olestra affected the ability to predict high calories based on the sensory properties of fat. These results extend the generality of previous findings that interfering with a predictive relationship between sensory properties of foods and calories may contribute to dysregulation of energy balance, overweight and obesity.     

Increased carbohydrate intake as a function of insulin administration in rats

Patterns of dietary self-selection were examined in male rats following subcutaneous injections of NPH insulin. Self-selection animals received separate dietary sources of protein, carbohydrate and fat, while single diet animals received ground Purina Rodent Chow. Food intakes and body weights were measured daily. In comparison to non-injected animals, both self-selection and single-diet animals displayed similar increases in caloric intakes and body weights in response to insulin administration. In animals maintained on the self-selection regime, the increase in caloric intake was solely a function of an increase in carbohydrate intake. Neither protein intake nor fat intake varied as a function of insulin administration. While fat intake remained stable in insulin-injected animals, non-injected self-selection animals gradually increased fat consumption throughout the experiment. Termination of insulin administration for all animals led to decreases in caloric intake below the levels of non-injected animals. Again, modification in caloric intakes in selecting animals were primarily a consequence of altered carbohydrate intake. Patterns of dietary self-selection in insulin-injected animals are contrasted to patterns of selection in other forms of experimental obesity.     

Diverse basal and stress-related phenotypes of Sprague Dawley rats from three vendors

Based on observed phenotypic differences in growth and ACTH responses to stress in Sprague Dawley rats obtained from different vendors, we ran head-to-head comparisons on rats obtained from three different vendors, Harlan, Charles River, and Simonsen, with respect to baseline phenotypic differences and a metabolic feedback hypothesis of hypothalamo-pituitary-adrenal (HPA) regulation. Charles River and Harlan rats gained weight faster than Simonsen rats, but chow intake standardized for body weight was not increased, consistent with their greater caloric efficiency. Weight gain was inversely related with mean daily temperatures, without differences in activity levels. Half of the animals given lard and 32% sucrose solutions in addition to chow increased caloric intake and core temperature, decreased caloric efficiency, and increased fat depots, leptin, and in Simonsen rats, insulin. A 5-day regimen of once-daily 2-h restraint decreased feeding and caloric efficiency. Rats from two vendors with the availability of sucrose and lard, Charles River and Simonsen, showed blunted HPA responses to restraint compared to chow controls, whereas the Harlans exhibited no adrenocorticotropin (ACTH) response and an amplified adrenocortical response on the high-energy diet compared to chow controls. Substantial phenotypic differences exist between Sprague Dawley rats from different vendors with respect to metabolism and HPA function. The metabolic feedback hypothesis was supported in two of the three vendors' rats.     

Dietary fat-induced hyperphagia in rats as a function of fat type and physical form

The influence of dietary fat on food intake and weight gain was assessed by feeding adult female rats diets that differed in the type and form of fat, as well as in the availability of other macro- and micronutrients. Compared to chow-fed controls, the various fat diets increased total food intake by 4% to 27%. Specifically, rats fed chow and a separate source of fat (fat option diet) consumed more fat and total calories, and gained more weight when the fat source was emulsified corn oil rather than pure corn oil or was vegetable shortening rather than corn oil. However, corn oil and shortening had similar effects on caloric intake and weight gain when presented as emulsified gels. Also, pure and emulsified-gel forms of shortening did not differ in their effects on caloric intake and weight gain. Supplementing the vegetable shortening with micronutrients, however, enhanced its hyperphagia-promoting effect. The results of two-choice tests revealed that the rats' preferences for the orosensory properties of the various fat sources did not account for the differential hyperphagias obtained. Rather, it appears that long-term fat selection and caloric intake are influenced primarily by postingestive factors. Fat selection and total intake were determined not only by the fat source itself, but also by the other diet options. That is, rats selected more fat and consumed more calories when chow was the alternative food than when separate sources of carbohydrate and protein were available.     

Selection of protein and fat by diabetic rats following separate dilution of the dietary sources

Diabetic and normal rats were allowed to select their diets from separate sources of protein, carbohydrate and fat. Following the determination of baseline intakes, diabetic and normal rats received dietary components in which either the protein (Experiment 1) or fat source (Experiment 2) was diluted by 25% or 50% by the addition of cellulose. Diabetic rats failed to maintain protein intake at both dilution levels, but made up for the loss of protein-derived calories by consuming more fat. Diabetic rats maintained fat intake at both dilution levels. Dietary dilutions had no effect on total caloric intakes or body weight gain of diabetic rats. Diabetic status, measured by fasting plasma glucose levels and urinary glucose excretion rates, also was unaffected by diet dilutions. These data suggest that diabetic rats maintain total caloric intake following dilution of either the protein or fat source of their diets, but defend intake of fat-derived calories more readily than protein-derived calories. Normal rats maintained both protein and fat intake at the 25% but not at the 50% dilution level. These findings are discussed in terms of the ability of diabetic rats to solve the metabolic problems associated with their diabetic condition.     

Sucrose intake as a function of its cost and the cost of chow

The avid consumption of pure carbohydrate solutions, which often results in a distortion of nutrient balance, is generally presumed to be driven by their taste. In the first of two experiments, we examined the effect of consumption cost on rats' intake of three concentrations of sucrose solution (8%, 16%, and 32%) when a nutritionally complete chow was concurrently freely available. In the second experiment, we examined the intake of 24% sucrose solution and chow as the consumption costs of both were varied. Increasing the cost of sucrose resulted in a reduction in the percent calories taken from sucrose; the steepness of the decline in intake with price was inversely related to the sucrose concentration and to the cost of chow. Chow calories were substituted for relatively expensive sucrose calories. An increase in the cost of chow resulted in a reduction in the percent of calories taken from chow and a protein-poor diet. The cost of sucrose did not affect the slope of the chow intake curve, presumably because, despite its sweet taste, sucrose was not a substitute for the protein, fat, and micronutrients in chow. Total caloric intake was conserved in all cases.

Thus, the avid consumption of sucrose solution is curtailed when it is costly; but the degree of change in intake with cost depends on the cost of an alternative food. These results suggest that diet selection involves a comparison not only of the taste and post-ingestive consequences of available foods, but also of the cost of calories and nutrients in the foods. Selection appears to be guided first by caloric requirements and the relative cost of calories, then by nutrient requirements and the relative cost of nutrients, and finally by taste.