Probing the causes of high-fat diet hyperphagia: a mechanistic and behavioral dissection.

High-fat diets promote hyperphagia in both rats and humans; however, understanding of the process by which dietary fat increases intake is incomplete. Since altering the fat content of a diet simultaneously changes both its sensory properties and postingestive effects, it is unclear whether high-fat diet hyperphagia is driven by oral influences, postingestive factors, or both. Previous findings from both animal and human studies indicate that relatively "less palatable" high-fat diets are overeaten relative to high-carbohydrate diets, indicating that the postingestive effects of high-fat foods are sufficient to promote hyperphagia. A program of research on rats is described, which isolates and assesses the independent effects of sensory and postingestive influences on intake of liquid high-fat and high-carbohydrate diets. An integrated series of experiments investigates both short-term (meal size, postprandial satiety) and long-term (ad lib intake over weeks) effects of diet composition on intake in order to "dissect" the causes of high-fat diet hyperphagia. Preliminary findings from this approach indicate that the postingestive effects of a high-fat diet promote longer meal size, less postprandial satiety per calorie, and greater daily calorie intake than a high-carbohydrate diet.

Role of dietary fat in calorie intake and weight gain.

This paper reviews the literature on the role of dietary fat in calorie intake and body weight gain in humans and laboratory animals. An overview of 40 animal studies which compared growth on high-fat (HF) and high-carbohydrate (HC) solid/powdered diets indicated that the HF diet elicited greater weight gain in 33 out of 40 studies. Enhanced growth on the HF diet was often, but not exclusively, attributable to greater caloric intake. Additional evidence for the growth-enhancing effect of HF diets emerges from "diet option" and "supermarket" feeding studies in rats, and experimental and epidemiological studies in humans. Three principal factors that contribute to the different responses to HF and HC diets are (a) caloric density, (b) sensory properties and palatability, and (c) postabsorptive processing. It is concluded that both calorie intake and metabolic energy expenditure are biased towards weight gain when a HF diet is consumed, and that the high caloric density of high-fat diets plays a primary role in weight gain. Humans may be biologically predisposed to gain weight when a HF diet is consumed.

Flavor enhancement of foods for the elderly can reverse anorexia.

Impairment of the senses of taste and smell is one of the major factors contributing to anorexia in the elderly. Anorexia often remits when foods are amplified by additional odor to compensate for diminished chemosensory functioning.

Gustatory and olfactory dysfunction in dementia: not specific to Alzheimer's disease.

Significant losses in the ability to detect the taste of glutamic acid and to recognize odorants were found in demented patients when compared with age-matched controls. These losses were not specific to patients with Alzheimer's disease (AD) but were also found in demented patients without AD. Detection thresholds for bitter-tasting quinine HCl were not higher in demented patients than in age-matched controls but were higher than thresholds in young subjects. These data suggest that losses in taste in demented patients may vary with the chemical structure of the tastant. The degree of loss in the ability to recognize odorants was greater in patients with a family history of senile dementia.

Carboxylic acid replacement structure-activity relationships in suosan type sweeteners. A sweet taste antagonist. 1.

N-(4-Cyanophenyl)-N'-(2-carboxyethyl)urea (2), an analogue of suosan [1,N-(4-nitrophenyl)-N'-(2-carboxyethyl)urea], is a known high-potency sweetener derived from beta-alanine. Sulfonic and phosphonic acid analogues of 2 were prepared to develop structure-activity relationships through modification of the carboxylic acid region of this family of sweeteners. Neither of the carboxylic acid replacements resulted in sweet analogues. However, we found that N-(4-cyanophenyl)-N'-[(sodiosulfo)methyl]urea (7) is an antagonist of the sweet taste response. The bitter taste response to caffeine, quinine, and naringin was also antagonized. Antagonist 7 was found to inhibit the sweet taste perception of a variety of sweeteners. Antagonist 7 had no effect on the sour or salty taste response.

Use of flavor-amplified foods to improve nutritional status in elderly patients.

Impairment of taste and smell perception can lead to decreased food intake in the elderly. The losses in chemosensory functioning can result from normal aging, disease state, drugs, and environmental pollutants. Experimental investigations are underway to develop practical taste enhancers. Clinical studies suggest that the addition of odors to foods to compensate for diminished chemosensory functioning is often helpful in increasing intake of nutrient-dense foods in older persons.

Detection thresholds of potassium salts are related to the molar conductivity of the anion.

In a previous study, we found that human taste detection thresholds for Na+ salts were linearly correlated with molar conductivity values at infinite dilution of their anions. In the present study, detection threshold concentrations for potassium salts were also found to be linearly correlated (r = -0.92) with the molar conductivity of the anion of the salt. Detection thresholds were determined here for nine potassium salts with the same anions as the sodium salts previously tested. The mean detection thresholds for these potassium salts were found to be: K Acetate (0.00311 M), K Carbonate (0.00286 M), K Chloride (0.00242 M), K Citrate (0.000300 M), K Phosphate (0.00196 M), K Sulfate (0.00090 M), K Tartrate (0.00164 M), K Glutamate (0.00153 M), and K Ascorbate (0.00375 M). The rank order correlation between the detection threshold values for sodium and potassium salts was 0.88. This finding suggests that detection thresholds for both Na+ and K+ salts are determined by the charge mobility of the anion.

Bitterness of sweeteners as a function of concentration.

Sixteen trained tasters provided sweetness and bitterness intensity ratings for 19 compounds including: acesulfame-K, alitame, aspartame, fructose, glucose, glycine, lactitol, maltitol, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone, neosugar (fructo-oligosaccharide), palatinit (isomalt), rebaudioside-A, sodium cyclamate, sodium saccharin, stevioside, sucralose, sucrose, and thaumatin. With increasing concentration, high-potency sweeteners including acesulfame-K, neohesperidin dihydrochalcone, sodium saccharin, rebaudioside-A, and stevioside tended to become more bitter. Low-potency sweeteners including fructose, sucrose, and lactitol tended to become less bitter with increasing concentration.

Sensory evaluations of fat-sucrose and fat-salt mixtures: relationship to age and weight status.

Young (mean age 22.4 years) and elderly (mean age 82.3 years) subjects tasted and rated a range of liquids containing between 0.5% and 36% dairy fat by weight. The liquids also contained either sucrose (0-20%) or NaCl (0-0.584%). Within each age group both normal weight and overweight subjects participated. The fat content in the mixtures was unrelated to pleasantness ratings for elderly subjects. The concentrations of both fat and sucrose in the mixtures determined the hedonic responses of young normal weight subjects. Overweight young subjects' hedonic responses were predominantly influenced by sucrose concentration. Fat content in dairy-salt mixtures was significantly related to pleasantness ratings by young subjects, but did not influence ratings by elderly subjects. These findings suggest that the elderly can significantly reduce dietary fat intake without sacrificing perceived pleasantness.

Flavor-calorie relationships: effect on weight gain in rats.

The effects of flavor variety, caloric density variety, and inconsistency of flavor-caloric density relationships on caloric intake and weight gain were studied in 36 young male rats. Lab chow was diluted with cellulose to produce three foods that differed in caloric density while having identical nutritional composition. High-density (HD) food contained 3.33 kcal/g; mid-density (MD) food contained 2.64 kcal/g; low-density (LD) food contained 2.06 kcal/g. These foods were flavored with nonnutritive powders and were used in four different feeding regimens. For 15 days, group FLAV ate MD with one of 3 flavors added daily in a 3-day rotation. Groups DENS and NOVEL rotated daily among LD, HD, and MD. One of three flavors was added to each food. For group DENS, LD always contained one flavor, MD always contained another flavor, and HD always contained the third flavor. For group NOVEL, flavor-density pairings were not consistent. A control group, CONT, ate only MD with a single flavor. Weight gain was greatest in group NOVEL. Neither density variety nor flavor variety alone enhanced weight gain relative to control. In a subsequent experiment, group NOVEL did not display a preference for a glucose-paired flavor. These results suggest that reduced orosensory control of energy balance induced by uncoupling of flavor-calorie relationships contributes to weight gain.

Flavor-postingestive consequence associations incorporate the behaviorally opposing effects of positive reinforcement and anticipated satiety: implications for interpreting two-bottle tests.

Rats consuming distinctively flavored solutions containing different numbers of calories learn to associate each flavor with the ensuing postingestive effects ("flavor-postingestive consequence learning"). The hallmark of such learning is preferential consumption of one of the flavors in two-bottle tests (both flavors presented in nutrient-identical solutions). Two experiments were conducted to characterize the relationship between the number of calories associated with flavors and subsequent preferences in two-bottle tests. In Experiment 1, three groups of rats each associated distinctive flavors with real-fed sugar and with sham-fed sugar. The groups differed in the concentration of sucrose (8%, 14%, 24%) with which they were trained. In two-bottle tests rats trained with 8% sucrose preferred the real-fed flavor, whereas rats trained with 24% sucrose preferred the sham-fed flavor. Rats trained with 14% sucrose were intermediate to the other groups. In Experiment 2, two groups of rats associated distinctive flavors with two concentrations of real-fed sucrose. In two-bottle tests, the group trained with 1% and 5% sucrose preferred the flavor paired with the higher concentration, whereas the group trained with 5% and 30% sucrose preferred the flavor paired with the lower concentration. These findings suggest that flavor-postingestive consequence learning incorporates both positive reinforcement, which has the behavioral effect of increasing intake of the associated flavor, and anticipated satiety, which has the behavioral effect of suppressing intake of the associated flavor. When a flavor is associated with relatively few calories, the positive reinforcing effect predominates over anticipated satiety. However, when a flavor is associated with a greater number of calories, anticipated satiety predominates over the positive reinforcing effect.

Dissociation of palatability and calorie effects in learned flavor preferences.

Rats acquire a preference for a flavor paired with a caloric solution over a flavor paired with a solution providing fewer or no calories. Because the palatability and the caloric value of the solutions typically covary, it is unclear which property of the high-calorie solution reinforces the flavor preference. Two studies were conducted to assess the independent effects of palatability and calories in flavor preference conditioning. In Experiment 1, rats consumed two distinctively flavored solutions having equal palatability but different caloric value. The flavor paired with ingestion of more calories was subsequently preferred, indicating that a caloric advantage is sufficient to establish a flavor preference (flavor-calorie conditioning). In Experiment 2, rats consumed two distinctively flavored solutions having equal calories but different palatability. The flavor paired with the more palatable solution was subsequently preferred, indicating that a palatability advantage is sufficient to establish a flavor preference (flavor-flavor conditioning). This finding demonstrates flavor-flavor conditioning in the context of postingestive stimulation by calories. Taken together, these results demonstrate both flavor-calorie and flavor-flavor conditioning in the context of normal ingestion (i.e., self-paced oral intake of nutritive solutions).

Effect of flavor enhancement of foods for the elderly on nutritional status: food intake, biochemical indices, and anthropometric measures.

The irreversible declines in taste and smell acuity that occur in many elderly persons can contribute to inadequate food intake and nutrition that are prevalent among the aged. Although chemosensory deficits cannot be reversed, previous studies have shown that the addition of intense flavors to foods can compensate for perceptual losses and improve food palatability and acceptance. In this study, the effect of sustained (3 week) flavor enhancement of typical institutional foods on the diet, health, and well being of 39 elderly (average age 84.6 SE 0.81 years) retirement-home residents was evaluated. For 3 weeks subjects ate an institutional diet (unenhanced). During another 3-week period, the same subjects ate identical foods to which intense flavors were added (enhanced). The 39 subjects were tested in two groups. For group 1 the unenhanced food period preceded the enhanced food period. For group 2, the order was reversed. Food intake was measured every weekday throughout the study, and the nutritional composition of the diet was analyzed. Biochemical measures of health status were obtained at the beginning of the study (baseline) and following both the unenhanced and enhanced periods. These measures included somatomedin-C/insulin-like growth factor I, transferrin, total T- and B-lymphocytes, and routine blood chemistries. Weight, height, midarm circumference, and triceps skinfold thickness were also measured. Handgrip strength and pinch strength were measured in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Relationship of dietary fat content to food preferences in young rats.

Weanling rats were fed either a high-fat (30% of calories) or a low-fat (10% of calories) diet for four weeks, after which fat preference was assessed using a choice paradigm. Fat preference was measured during 2-hour intake tests in which three peanut butter/peanut oil mixtures containing 0.50, 0.61, and 0.71 grams fat/gram were offered to each animal. Rats fed the high-fat (HF) diet preferred the highest-fat mixture and consumed more total fat during intake tests than animals fed the low-fat (LF) diet. Intake of NaCl and sucrose solutions was measured during separate intake tests. LF-fed rats drank more NaCl solution than HF-fed rats. Following these tests a subgroup of the LF-fed animals was fed the HF diet, and a subgroup of the HF-fed group was fed the LF diet for a further four weeks. Upon repetition of the intake tests, rats that had been fed the HF diet during the initial four weeks still preferred the highest-fat mixture.

Learned suppression of intake based on anticipated calories: cross-nutrient comparisons.

Following training with distinctively flavored solutions which differ in calories and thus in their postingestive effects, rats demonstrate flavor-postingestive consequence learning by preferentially consuming one of the flavors in two-bottle tests (both flavors presented in nutrient-identical solutions). The direction of the preference--for the flavor previously paired with more calories (F-hi) or for the flavor previously paired with fewer calories (F-lo)--depends critically upon the magnitude of postingestive effects experienced during training. The most frequent and more thoroughly investigated observation has been preferential consumption of F-hi (conditioned flavor preference). However, when relatively concentrated solutions (e.g., 5% and 30% sucrose) are used as the training nutrients, F-lo is preferentially consumed in two-bottle tests. This lesser intake of F-hi presumably reflects its previous association with the more potent satiating effect of the highly concentrated nutrient: conditioned satiety. The present series of experiments explored conditioned satiety across nutrient types. In each experiment, rats consumed 30 mL of distinctively flavored nutritive solution per day, alternating between a distinctively flavored high-calorie (1.6 kcal/mL) solution and a lower calorie (0.2 kcal/mL) solution containing a different flavor. Two-bottle testing evaluated whether conditioned satiety was evident. Experiment 1 found that rats trained with sucrose, fructose, glucose, maltodextrin, or saccharin-sweetened medium-chain triglyceride oil emulsion preferentially consumed F-lo in two-bottle tests. In contrast, rats trained with corn oil emulsions tended to preferentially consume F-hi. In Experiment 2, increasing the number of corn oil calories associated with F-hi produced a tendency toward preferential intake of F-lo in two-bottle tests. In Experiment 3, rats consumed a high-fat maintenance diet; sucrose-trained rats again consumed more F-lo than F-hi, whereas rats trained with corn oil emulsions showed a tendency (nonsignificant) to consume more F-lo in two-bottle tests. In Experiment 4, however, adding saccharin to corn oil emulsions did produce conditioned satiety. These findings demonstrate conditioned satiety as a robust phenomenon across various nutrient types; however, corn oil calories entrain conditioned satiety only under certain conditions.

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.

Taste and smell sensations enhance the satiating effect of both a high-carbohydrate and a high-fat meal in humans.

The effects of meal sensory properties (tasty vs. bland) and nutrient composition [high-CHO (carbohydrate) vs. high-FAT] on hunger ratings, blood glucose and free fatty acids (FFA), taste perception, and subsequent food intake, were studied in human subjects. Aspartame and vanilla were used to augment meal palatability, yielding four isocaloric liquid meals: bland-FAT, tasty-FAT, bland-CHO, tasty-CHO. Normal-weight, nondieting young adults consumed each of the meals for breakfast on separate days. The main finding was that tasty versions of high-FAT and high-CHO meals were more satiating than nutritionally identical bland meals, as indicated by a greater decrease in hunger ratings following the tasty meals. Changes in blood glucose and FFA were related to meal nutrient composition, but not to meal sensory properties. High-CHO meals tended to be more satiating than high-FAT meals. Consumption of each of the meals produced a similar decrease in pleasantness ratings of food-related tastes. Intake of carbohydrates was significantly higher at a self-selected lunch 5.25 h following a tasty breakfast. These findings indicate that hunger is decreased to a greater extent by meals flavored with aspartame and vanilla relative to nutritionally identical, unflavored meals. The satiety-enhancing effect of oral stimulation was found for both high-FAT and high-CHO meals.

Adaptation of sweeteners in water and in tannic acid solutions.

Repeated exposure to a tastant often leads to a decrease in magnitude of the perceived intensity; this phenomenon is termed adaptation. The purpose of this study was to determine the degree of adaptation of the sweet response for a variety of sweeteners in water and in the presence of two levels of tannic acid. Sweetness intensity ratings were given by a trained panel for 14 sweeteners: three sugars (fructose, glucose, sucrose), two polyhydric alcohols (mannitol, sorbitol), two terpenoid glycosides (rebaudioside-A, stevioside), two dipeptide derivatives (alitame, aspartame), one sulfamate (sodium cyclamate), one protein (thaumatin), two N-sulfonyl amides (acesulfame-K, sodium saccharin), and one dihydrochalcone (neohesperidin dihydrochalcone). Panelists were given four isointense concentrations of each sweetener by itself and in the presence of two concentrations of tannic acid. Each sweetener concentration was tasted and rated four consecutive times with a 30 s interval between each taste and a 2 min interval between each concentration. Within a taste session, a series of concentrations of a given sweetener was presented in ascending order of magnitude. Adaptation was calculated as the decrease in intensity from the first to the fourth sample. The greatest adaptation in water solutions was found for acesulfame-K, Na saccharin, rebaudioside-A, and stevioside. This was followed by the dipeptide sweeteners, alitame and aspartame. The least adaptation occurred with the sugars, polyhydric alcohols, and neohesperidin dihydrochalcone. Adaptation was greater in tannic acid solutions than in water for six sweeteners. Adaptation of sweet taste may result from the desensitization of sweetener receptors analogous to the homologous desensitization found in the beta adrenergic system.