Dietary self-selection in chronically insulin-treated golden hamsters

Adult male golden hamsters were maintained on either Purina Rat Chow (chow group) or a self-selection diet consisting of high-protein chow, pure carbohydrate, and pure fat (choice group). Animals were injected for 12 consecutive days with either long-acting insulin (20 U/kg for 4 days, 60 U/kg for 4 days, and 100 U/kg for 4 days) or physiological saline. Insulin-injected hamsters under both dietary conditions increased their total caloric consumption by up to 33% and gained significantly more weight than saline-injected controls. Choice hamsters increased their fat intake in response to the 60 and 100 U/kg doses of insulin, but carbohydrate and protein consumption increased only in response to the 100 U/kg dose. Choice hamsters derived approximately 65% of the excess calories ingested during insulin administration from fat, but only 20% from carbohydrate and 15% from protein. Results are related to those previously observed in other species.     

Dietary self-selection of golden hamsters in response to acute food deprivation and chronic food restriction

Adult male golden hamsters were maintained on either Purine Rat Chow (Chow diet) or a self-selection diet consisting of high-protein chow, pure fat, and pure carbohydrate (Choice diet). In Experiment 1, animals were deprived of food for single periods of up to 48 hr. Animals on the Chow diet did not increase intake at any time after deprivation; animals on the Choice diet selectively increased their consumption of fat-derived calories and increased their total caloric intake during the first 6 hr of refeeding, but not thereafter. The nature of the diet did not influence the rate at which animals regained weight following deprivation. In Experiment 2, hamsters were placed on food-restriction schedules (access to food either for 1 hr/day only or on alternate days only) until they lost 20% of starting body weight. Chow-fed animals demonstrated little or no change in food intake either during or after food restriction. Hamsters on the Choice diet consumed more calories and lost weight more slowly than did chow-fed animals during 1-hr/day feeding; intake of fat-derived calories was elevated during restriction. Choice hamsters increased total caloric intake only towards the end of the alternate-days restriction schedule. Choice hamsters were hyperphagic following both types of food-restriction schedules, but no increased preference for fat-derived calories was observed. Factors influencing food consumption of hamsters in response to deprivation and restriction are discussed.     

Voluntary ethanol consumption and obesity in golden hamsters

Adult male golden hamsters with continuous access to Purina chow, water and either 15, 30 or 45% ethanol (v/v) for 14 weeks derived an average of 34, 37 and 22%, respectively, of their total calories from ethanol. Animals in the 15 and 45% ethanol groups derived up to 12.0 and 9.9 kcal/day, respectively, from ethanol, but the Purina chow intakes of these animals were such that their total caloric consumption and their body weights did not significantly exceed those of a control group having access only to Purina chow and water. In contrast, the 30% ethanol group derived up to 16.4 kcal/day from ethanol, and consistently consumed 25% more total calories than the control group, despite eating significantly less Purina chow. Furthermore, hamsters in the 30% ethanol group were 27% heavier and had significantly larger epididymal and retroperitoneal fat pads than controls. Similarities are noted between ethanol-induced obesity in hamsters and the dietary obesity which has been observed in rats having continuous access to Purina chow and a 32% sucrose solution.     

Control of protein intake in golden hamsters

Experiments were performed to investigate the behavioural responses of golden hamsters to manipulations of dietary protein availability. In the first experiment, hamsters were maintained on a protein-free diet and a powdered diet containing 64.8% protein (P64.8). When the P64.8 diet was progressively diluted with cornstarch, hamsters increased their intake of this diet fraction, but protein intake nevertheless declined. When the protein content of the diet was 16.2%, animals derived only 6% of total calories from protein and lost weight despite normal intake of calories. In the remaining experiments, hamsters were maintained on a self-selection regimen of high-protein chow, pure carbohydrate (sugar cubes), and pure fat (vegetable shortening). When high-protein chow was removed for either 5 or 10 days, total caloric intake and body weight declined, and hamsters selectively increased protein intake for several days after high-protein chow was returned. Hamsters allowed access to high-protein chow for only one hour each day markedly increased the amount of high-protein chow they ate during this hour as protein-restriction continued, but still consumed only about 10% of their normal daily protein intake on this schedule and lost 20% of starting body weight in two weeks; when free access to high-protein chow was restored, these animals selectively increased their protein intake above pre-restriction levels. Hamsters given access to high-protein chow only on alternate days demonstrated a relatively modest and slowly developing increase in protein intake, perhaps because they incurred only a moderate protein deficit. The results suggest that when protein intake falls below normal minimum requirements, hamsters will demonstrate an adaptive protein hunger but make only a limited adjustment to the dilution of a protein-containing diet fraction.     

High-fat hyperphagia in neurotrophin-4 deficient mice reveals potential role of vagal intestinal sensory innervation in long-term controls of food intake

Neurotrophin-4 (NT-4) deficient mice exhibit substantial loss of intestinal vagal afferent innervation and short-term deficits in feeding behavior, suggesting reduced satiation. However, they do not show long-term changes in feeding or body weight because of compensatory behaviors. The present study examined whether high-fat hyperphagia induction would overcome compensation and reveal long-term effects associated with the reduced vagal sensory innervation of NT-4 mutants. First, modifications of a feeding schedule previously developed in rats were examined in wild-type mice to identify the regimen most effective at producing hyperphagia. The most successful schedule, which was run for 26 days, included access to a 43%-fat diet and pelleted chow every other day and access to only powdered chow on the alternate days. On high-fat access days mice consumed 25% more calories than mice with continuous daily access to the same high-fat diet and pelleted chow. This feeding regimen also induced hyperphagia in NT-4 deficient mice and their wild-type controls: on high-fat exposure days mutants consumed 35% more calories relative to continuous-access mutants, and wild types ate 25% more than continuous-access wild types. Moreover, on high-fat access days the alternating NT-4 mutants significantly increased caloric intake by 9% compared to alternating wild types. Thus, high-fat hyperphagia appeared to override compensation, permitting short-term changes in meal consumption by mutants that accrued into long-term changes in total daily food intake. This raises the possibility that intestinal vagal sensory innervation contributes to long-term, as well as to short-term regulation of food intake.     

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.     

Effects of dietary sugar and of dietary fat on food intake and body fat content in rats

The long term ingestion of a sugar-rich diet (low fat) caused severe obesity in adult rats. In a separate experiment, the habitual consumption of a fat-rich diet (40% kcal from fat) also caused severe obesity. Severe obesity developed in both groups of animals even though they did not overeat. Voluntary food intake for the sugar-fed rats averaged 28,314 +/- 756 calories/rat per 55 wks which was similar to the value of 28,884 +/- 953 calories/rat per 55 wks for the fat-fed rats. However, both values were lower than that of 32,869 +/- 588 for the control rats eating Purina chow. Despite a lower caloric intake, carcass fat averaged 45 +/- 1% for rats eating the sugar-rich diet and 46 +/- 2% for rats eating the fat-rich diet, but only 33 +/- 2% for rats eating a diet of Purina chow. These results provide evidence that severe obesity can develop in the absence of hyperphagia in animals eating a sugar-rich or fat-rich diet. Finally, a rat model for severe obesity is presented in which carcass fat ranged from 18% (lean) to 61% (severe obesity) using dietary intervention alone at critical stages of the animal's life.     

Differential effects of sucrose and fructose on dietary obesity in four mouse strains

We examined sugar-induced obesity in mouse strains polymorphic for Tas1r3, a gene that codes for the T1R3 sugar taste receptor. The T1R3 receptor in the FVB and B6 strains has a higher affinity for sugars than that in the AKR and 129P3 strains. In Experiment 1, mice had 40 days of access to lab chow plus water, sucrose (10 or 34%), or fructose (10 or 34%) solutions. The strains consumed more of the sucrose than isocaloric fructose solutions. The pattern of strain differences in caloric intake from the 10% sugar solutions was FVB > 129P3 = B6 > AKR; and that from the 34% sugar solutions was FVB > 129P3 > B6 ≥ AKR. Despite consuming more sugar calories, the FVB mice resisted obesity altogether. The AKR and 129P3 mice became obese exclusively on the 34% sucrose diet, while the B6 mice did so on the 34% sucrose and 34% fructose diets. In Experiment 2, we compared total caloric intake from diets containing chow versus chow plus 34% sucrose. All strains consumed between 11 and 25% more calories from the sucrose-supplemented diet. In Experiment 3, we compared the oral acceptability of the sucrose and fructose solutions, using lick tests. All strains licked more avidly for the 10% sucrose solutions. The results indicate that in mice (a) Tas1r3 genotype does not predict sugar-induced hyperphagia or obesity; (b) sucrose solutions stimulate higher daily intakes than isocaloric fructose solutions; and (c) susceptibility to sugar-induced obesity varies with strain, sugar concentration and sugar type.     

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.     

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.     

Obesity without overeating in golden hamsters

When male golden hamsters were switched from a diet of Purina rodent chow to a calorically-dense high-fat diet or were given ad lib access to a 32% sucrose solution in addition to chow, they adjusted their food intakes rapidly (within 24 hr) and did not overeat. Nevertheless, the fat-fed hamsters tripled their rate of weight gain and nearly doubled their carcass fat content after one month on the diet. Resting oxygen consumption (animals awake but quiet) was significantly lower in fat-fed animals than in chow-fed controls. Sucrose feeding had no effect on food intake, body weight gain, carcass composition or oxygen consumption. Thus, whereas rats exhibit dietary obesity in spite of increases in energy expenditure (diet-induced thermogenesis), fat-fed hamsters seem to become obese because of decreases in energy expenditure. However, although actual energy expenditure is reduced, fat-fed hamsters exhibit an enhanced thermogenic capacity. Interscapular brown adipose tissue mass, protein content, and DNA content as well as norepinephrine-stimulated oxygen consumption were all significantly elevated in fat-fed hamsters. The significance of these concurrent diet-induced decreases in energy expenditure and increases in thermogenic capacity is not clear, but they could be of some value in preparing the hamster for winter.     

Regulation of caloric intake in yellow mice (C57BL/6J-Ay/alpha).

The ability of yellow and normal black mice to reduce food intake when given surplus calories was studied to elucidate the mechanisms responsible for hyperphagia in yellow mice. When given sugar solutions to drink, immature (6–7 weeks old) yellow mice increased total caloric intake more than did lean control mice. Older (11–14 weeks) yellow mice were similar to control mice. The oldest yellow mice tested (25–33 weeks) increased total caloric intake less than lean control mice, when given sugar solutions. In contrast, yellow mice of all ages increased total caloric intake more than lean mice when given corn oil. Yellow mice had similar or lower preference for sugar and oil calories than did black mice.     

Effects of thirst-inducing stimuli on consumption of ethanol solutions by golden hamsters

Two experiments were performed to examine the acute effects of thirst-inducing stimuli upon the intake of tap water and ethanol solutions by golden hamsters, a species which avidly consumes ethanol solutions. In Experiment 1, three groups of adult male hamsters (n = 6/group) were maintained on Purina chow and tap water; hamsters in two of the groups also had access to one of two ethanol solutions (15% or 30%, v/v). Animals were deprived at various times of either one or both fluids for 24 hr, and then either one or both fluids were presented during a 2-hr drinking test. Total water intake increased substantially following both selective water deprivation and total fluid deprivation whenever tap water was available during the drinking test, but no significant changes occurred when only the ethanol solution was available. Both total fluid deprivation and selective ethanol deprivation produced similar increases in ethanol consumption, but selective water deprivation did not, suggesting that the temporary removal of tap water has little direct effect upon ethanol intake in hamsters, at least at the ethanol concentration levels studied here. In Experiment 2, thirst was induced by a subcutaneous injection of 10% saline (1 ml/100 g). This procedure produced large increases in total water intake whenever tap water was available during the drinking test, but ethanol intake did not change under any circumstances. These results suggest that factors that acutely enhance water intake have little or no effect upon the ethanol consumption of golden hamsters.     

Feeding in response to repeated protamine zinc insulin injections

Sustained overeating was induced in rats with repeated daily injections of protamine zinc insulin. The hyperphagia and hypophagia upon termination of insulin treatment were directly related to the amount of insulin that had been administered. The intake was regulatory since animals adjusted food consumption appropriately to compensate for caloric intake from glucose solutions, and they maintained stable caloric intake by reducing the weight of food ingested from a high fat diet. Overeating was unmodified by the use of an equicaloric high protein diet even though total weight gain was reduced. Injections of cycloheximide and dexamethasone prevented protamine zinc insulin induced overeating.     

Caloric compensation following insulin administration in rats

Caloric intakes following injections of insulin were examined in male rats maintained on diets of different caloric densities. Following saline or insulin injections, food intake was measured every two hours for six hours or food was withheld for six hours until recovery of normo-glycemia and total intake was measured at seven and eight hours post-injection. Additionally, levels of plasma metabolic fuels, liver glycogen and stomach contents were measured following saline and insulin injections. Animals in both the continuous and delayed access conditions consumed the same number of calories following injections of insulin. Similarly, the increases in intake relative to saline baseline conditions were comparable across diet groups in both conditions although animals tested in the delayed access paradigm were less variable in their response. Changes in levels of metabolic fuels, stomach contents and liver glycogen were found to be consistent with the known effects of insulin and counter-regulatory responses to the induced hypoglycemia.     

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.     

Role of caloric homeostasis and reward in alcohol intake in Syrian golden hamsters

The Syrian golden hamster drinks alcohol readily, but only achieves moderate blood alcohol levels, and does not go through withdrawal from alcohol. Because the hamster is a model of caloric homeostasis, both caloric content and reward value may contribute to the hamster's alcohol consumption. The current study examines alcohol consumption in the hamster when a caloric or non-caloric sweet solution is concurrently available and caloric intake in the hamster before, during, and after exposure to either: alcohol, sucrose or saccharin. In Experiments 1 and 2, hamsters were given access to alcohol (15% v/v) and water; once alcohol consumption steadied, a bottle containing an ascending concentration of sucrose (99-614 mM) or saccharin (2-10 mM), or water was added. In Experiment 3, hamsters were given access to alcohol (15% v/v), sucrose (614 mM), saccharin (4 mM), or a second water bottle for 14 days. After the second bottle was removed, measurements continued for 14 days. Sucrose exposure suppressed alcohol consumption at concentrations lower in calories than the alcohol solution. Saccharin exposure failed to suppress alcohol consumption. Exposure to sucrose and alcohol but not saccharin decreased food intake. Decreased alcohol consumption in response to a caloric sweetener and decreased food intake during alcohol exposure support that alcohol consumption by the hamster is mediated by caloric content. However, suppression of alcohol intake by a sucrose solution of lower caloric content and the equivalent intake of individual alcohol, sucrose and saccharin solutions support a role for reward value in alcohol consumption.     

Suppression of food intake in diabetic rats by voluntary consumption and intrahypothalamic injection of glucose

When given a choice between 2 concentrations of glucose (5 and 35%) normal rats prefer to consume most of their glucose from the concentrated source while diabetics prefer the dilute source. Although both consume approximately the same total amount of glucose, on a caloric basis the glucose depressed chow intake more in diabetics than in normal rats, indicating that diabetics can experience the satiating effects of glucose. Also, since the diabetics excreted more glucose in urine during the glucose access, the overall retention of calories appeared to be less than of controls, indicating the diabetics are effectively hypophagic as compared to controls when they ingested large quantities of glucose. Direct injection of glucose into the ventromedial hypothalamus suppressed feeding as effectively in diabetics as in controls, indicating that normal titers of insulin are probably not necessary for suppression of feeding by ingested glucose in diabetic animals.     

Food consumption, plasma glucose and stomach-emptying in insulin-injected hamsters

Two experiments were performed to investigate whether insulin-induced hyperphagia (IIH) serves an adaptive function in counteracting hypoglycemia in hamsters. In Experiment 1, insulin-injected hamsters having free access to food during a six-hour feeding test had neither higher plasma glucose (PG) concentrations nor lower frequencies of neurological impairment at the end of the test than did hamsters whose food intake was restricted to control levels. In Experiment 2, it was observed that PG fluctuations did not act as a trigger for meal-onset in insulin-injected hamsters, nor was PG affected by consumption of a meal during IIH. The withholding of food for periods longer than the typical intermeal interval (IMI) of insulin-injected hamsters (= 50 min) resulted in a marked increase in the frequency of neurological deficits among hamsters having PG levels lower than about 40 mg/dl. However animals with similarly low PG concentrations, but deprived of food for less than 50 min showed no signs of impairment, suggesting that some alternate metabolic fuel is available during the IMI and prevents the occurrence of behavioural deficits. The results of these experiments suggest that a simple glucostatic interpretation of IIH in hamsters is inadequate, and although hyploglycemia may play a role in hamster IIH, other factors must also be considered. In Experiment 3, the effect of a hyperphagia-inducing dose of insulin upon stomach emptying was investigated. It was found that both insulin-injected and control hamsters have similar amounts of food in their respective pregastric and gastric pouches at both the onset and offset of meals, but that both pouches empty far more rapidly under the influence of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new animal model of binge eating: key synergistic role of past caloric restriction and stress

Dieting and stress are important in the etiology and maintenance of eating disorders, and dieting strongly predicts stress-induced overeating in humans. We hypothesized that caloric restriction and stress interact in a unique manner to promote binge eating. To test this hypothesis, a group of young female rats were cycled through a restriction period (4 days of 66% of control food intake) followed by 6 days of free feeding prior to being stressed by acute foot shock. After three of these cycles, the food intake of rats exposed only to restriction (R), or only to stress (S), did not differ from controls. However, R+S rats that were restricted and refed, despite normal body weight and food intake after free feeding, engaged in a powerful bout of hyperphagia when stressed (Experiment 1). The R + S effect was replicated in an older group of rats (Experiment 2). The hyperphagia was characteristically binge-like, it constituted a 40% selective increase in highly palatable (HP) food (P < .001) over a discrete period of time (within 24 h post-stress), and reflected feeding for reward (higher HP:chow ratio) over metabolic need as occurred after restriction (higher chow:HP ratio). Subsequent experiments revealed that binge eating did not occur if only chow was available (Experiment 3) or if restriction-refeeding (R-R) did not proximally precede stress (Experiment 4). Experiment 5 revealed that a history of R-R cycles followed by only one stress episode was sufficient to increase intake to 53% above controls as early as 2 h after stress (P < .001). This animal model of binge eating should facilitate investigations into the neurochemical changes induced by dieting and environmental stress to produce disordered eating and provide a preclinical tool to test preventive strategies and treatments more relevant to bulimia nervosa, multiple cases of binge eating disorder (BED) and binge-purge type anorexia nervosa.