Original Article | Published:

High intake of palatable food predicts binge-eating independent of susceptibility to obesity: an animal model of lean vs obese binge-eating and obesity with and without binge-eating

International Journal of Obesity volume 31, pages 13571367 (2007) | Download Citation

Subjects

Abstract

Objective:

To determine the stability of individual differences in non-nutritive ‘junk’ palatable food (PF) intake in rats; assess the relationship of these differences to binge-eating characteristics and susceptibility to obesity; and evaluate the practicality of using these differences to model binge-eating and obesity.

Design:

Binge-eating prone (BEP) and resistant (BER) groups were identified. Differential responses to stress, hunger, macronutrient-varied PFs, a diet-induced obesity (DIO) regimen and daily vs intermittent access to a PF+chow diet, were assessed.

Subjects:

One hundred and twenty female Sprague–Dawley rats.

Measurements:

Reliability of intake patterns within rats; food intake and body weight after various challenges over acute (1, 2, 4 h), 24-h and 2-week periods.

Results:

Although BEP and BER rats did not differ in amount of chow consumed, BEPs consumed >50% more intermittent PF than BERs (P<0.001) and consistently so (α=0.86). BEPs suppressed chow but not PF intake when stressed, and ate as much when sated as when hungry. Conversely, BERs were more affected by stress and ate less PF, not chow, when stressed and were normally hyperphagic to energy deficit. BEP overeating generalized to other PFs varying in sucrose, fat and nutrition content. Half the rats in each group proved to be obesity prone after a no-choice high fat diet (DIO diet) but a continuous diet of PF+chow normalized the BEPs high drive for PF.

Conclusion:

Greater intermittent intake of PF predicts binge-eating independent of susceptibility to weight gain. Daily fat consumption in a nutritious source (DIO-diet; analogous to a fatty meal) promoted overeating and weight gain but limiting fat to daily non-nutritive food (PF+chow; analogous to a snack with a low fat meal), did not. The data offer an animal model of lean and obese binge-eating, and obesity with and without binge-eating that can be used to identify the unique physiology of these groups and henceforth suggest more specifically targeted treatments for binge-eating and obesity.

Introduction

There has been a growing appreciation for the role of highly PF in animal models of obesity and eating disorders. Intermittent intake of PF alone promotes subsequent binge-like eating;1, 2 it also interacts with caloric restriction3 and stress4, 5 to produce binge-eating;6, 7, 8 and it changes central reward substrates9, 10 in ways similar to that caused by drugs of abuse.2, 11, 12 It is also well known that palatable junk food contributes to passive overeating, weight gain and obesity in humans.13, 14, 15, 16, 17, 18 Many PFs have little or no nutritional value (dubbed ‘junk’ foods) yet are consumed daily as snacks and/or meals19 and are calorie dense, mainly because of a high amount of fat and sucrose kilocalories.20, 21, 22 Some individuals are more susceptible to higher intake of PF or have increased hedonic responses to PF. These traits have been associated with amount of later weight gain.23, 24, 25, 26

PF also plays a salient role in binge-eating among obese and normal weight individuals with binge-eating disorders. This population typically restricts their intake of PF, viewing it as ‘forbidden’. However, PF is highly craved, often triggers binge-eating and comprises a substantial part of the binge.18, 27, 28, 29, 30, 31 Binge-eating is also associated with heightened reward sensitivity, which may enhance drive for PF.10, 32

Less is known regarding whether a high drive for PF predisposes the development of maladaptive eating habits and obesity. Although we cannot model in animals all of the many factors that contribute to individual food preferences in humans, we can identify rats with that overconsume PF and determine whether this contributes to obesity and binge-eating or behaviors consistent with binge-eating characteristics in humans. Whether trait or state-related, the physiological mechanisms that mediate a high drive for PF are worth investigating. A valuable animal model for such studies would be one that differentiated rats with a high or low drive for PF and within those distinctions, rats that developed or resisted obesity. Rats with a high drive for PF but that did not develop obesity would help elucidate mechanisms that make it easier for some of us to maintain a healthy body weight despite frequent indulgence in PFs. This knowledge would ultimately help those that have a more difficult time regulating their appetite or body weight amidst our food-hedonic environment.

In working with rats and PF, we noted that although outbred Sprague–Dawley rats of the same age and gender consume very similar amounts of rat chow on a daily basis, the amount of PF they consume when given a choice between PF and chow on an intermittent basis was much more varied. Noticing such individual differences in PF intake, we thought it would be valuable to more closely explore and characterize individual differences in PF intake within groups of rats. To do so, we performed six behavioral experiments using a low-nutritive sweet and fat (sweet/fat) food, Oreo cookies, as the PF. We have used this food successfully in previous models of stress-induced binge eating.7, 10 Others have used a similar sweet/fat combination in their choice of PF (Reese's peanut butter chips) with the same animal model.8 The combination of sucrose and fat is a very common composition of many junk foods and their consumption is associated with increasing body mass index, particularly in women.16, 33

We first tested the consistency of a high vs low intake of PF pattern within rats (i.e., are high or low PF eaters always high or low PF eaters?), when PF was provided intermittently. We then explored how rats differing in the amount of PF consumed respond to environmental stress and to hunger (do they show different feeding responses to these manipulations?). We also assessed whether the different PF intake patterns in rats generalized to other PF foods of varying nutritional and macronutrient composition. Further, we examined whether differential PF intake predicted DIO or resistance (are high-PF eaters just DIO-prone rats?). Lastly, we assessed whether varying PF intake patterns might change if the rats had continuous access to a choice of PF food and chow, the combination used to distinguish the high vs low PF consumers.

The results yielded four stable and behaviorally distinct groups of rats that can be characterized as binge-eating obesity-prone, binge-eating obesity resistant, non-binge-eating obesity prone and non-binge-eating obesity resistant. We believe these groups can serve as a practical animal model with which to better understand the physiological differences underlying these clinical conditions and with which to understand the psychobiology of high vs low cravings for and intake of PF.

Methods

Experiment 1: Assignment of rats into BEP or BER groups

The purpose of Experiment 1 was to determine whether rats displayed a stable pattern of greater vs lower acute intake of PF, despite equivalent consumption of chow. A total of N=60, 90-day-old female Sprague–Dawley rats were acclimated to individual bedded cages under a 12/12 h light-dark cycle (lights on at 1100 h) with access to ad lib chow (Harlan Teklad Global Diets, Indianapolis, IN, USA) and water for 2 weeks. Four feeding tests were then conducted wherein all rats were given ad lib access to a choice of chow and a PF, Oreo Double Stuf cookies (Nabisco, East Hanover, NJ, USA) for a 24 h period. Each feeding test was followed by at least 3–5 days of only chow such that their access to the PF was intermittent. During the four feeding tests, the foods were given just before lights were put off and amounts consumed were measured after 1, 2, 4 and 24 h. For subsequent experiments, only 4 and 24 h intakes were recorded but the earlier hours measured here served to gauge how quickly the rats differed in amount of PF consumed. From the initial large (N=60) group, two groups were created based on their 4 h PF intake. The 4 h intake measure was chosen to determine the groups as it represents a discrete period of time and an interval in which we have consistently noted measurable binge-eating with previous models.6, 7, 10 First, the median kcal score for each 4 h cookie feeding tests was determined. At the end of the last test, the rats were placed into BEP or BER categories for each test depending on whether they ate more or less of the median score. Then, the 20 most consistently high PF intake rats and the 20 most consistently low PF intake rats were assigned BEP or BER status, respectively. The remaining rats represented the middle-most PF consumers and were used only for comparative reasons in some of the subsequent tests. On days between the feeding tests, when rats were given only chow, 4 and 24 h intakes were also recorded to confirm that the groups did not differ in amount of chow consumed. This determined that any difference in the feeding behavior of the groups was expressed uniquely by PF; the groups were indistinguishable if fed only chow.

Experiment 2. Differences between BEP and BER feeding behavior in response to stress

To explore behavioral differences between BEPs and BERs beyond their spontaneous amount of PF intake, we asked if they might also differ in their feeding response to an environmental stressor. Stress was used to alter food intake under sated conditions. Specifically, it is known to cause hypophagia or hyperphagia in rats and humans.7, 8, 34 Following a week of chow-only feeding interrupted midweek by 1 day of PF+chow, half of the BEPs and half of the BERs (N=10/group) were subjected to four 3-sec bouts of 0.6 m-scrambled footshock at lights out (see Hagan et al.,7 for procedural and apparatus details). The other weight-matched rats of each group were placed in the shock alley for the same amount of time but no current was delivered. The rats were then returned to their home cages just before lights out with pre-measured PF and chow; intakes were recorded at 1, 2,4 and 24 h post dark-onset.

Experiment 3. Differences between BEP and BER feeding behavior in response to hunger

We also tested whether BEPs and BERs might differ in their feeding response to hunger. Hunger was used to precipitate a metabolic need that might be differentially met in BEPs and BERs. To test this, BEP and BER rats were assigned to either sated or hungry conditions after counterbalancing for previous experience with stress (i.e., an equal number of previously stressed and unstressed rats were represented in the hunger vs sated conditions). As in Experiment 2, this test was preceded by another week of chow-only feeding and a mid-week PF+chow day. On the day before the hunger test, rats in the hungry condition had their chow intake limited to 50% of their normal 24 h chow intake (determined from the previous chow-only day's mean intake). On the day of the test, all rats were given a premeasured amount of chow and PF; intakes were recorded as in Experiment 2.

Experiment 4: Stability of BEP/BER status when using different palatable foods

Experiments 4–6 used BEP and BER groups selected from a new group of N=60, 90-day-old female Sprague–Dawley rats. They were selected after four PF+chow feeding tests as described in Experiment 1. For this experiment, after a week of chow-only feeding, we substituted Oreo cookies as the PF for various other PFs differing in texture, macronutrient composition and nutritional value. A total of five food items were tested with a minimum of three chow-only days in between tests. The items, in order of presentation were a high-fat pellet diet typically used in DIO studies (Research Diets, Diet # D12266B, New Brunswick, NJ, USA; 4.41 kcal/g; 31.8% fat, 51.4% carbohydrate and 16.8% protein); Oreo-flavored pellets (specially formulated by Research Diets, NJ, USA; 4.6 kcal/g; 20.3% fat, 64.2% carbohydrates and 4.6% protein); Froot Loops (Kellogg, Battlecreek, MI, USA; 3.93 kcal/g; 4% fat, 88% carbohydrate and 3.3% protein); candy corn (Brach's Confections, Chattanooga, TN, USA; 3.6 kcal/g; 100% carbohydrate); and Crisco All-Vegetable Shortening (Proctor & Gamble, OH, USA; 9.2 kcal/g; 100% fat). For comparison, regular chow (Harlan Teklad Global Diets, Indianapolis, IN, USA) contains 3.3 kcal/g; 3.5% fat, 69.8% carbohydrate and 16.7% protein and the Double Stuf Oreo cookies (Nabisco, East Hanover, NJ, USA), used to discern BEPs from BERs, contain 4.8 kcal/g; 24% fat, 72% carbohydrate and 3.4% protein. A generous premeasured amount of one type of PF at a time was given with chow and water to all BEP and BER rats at lights out. Intake was measured after 4 and 24 h. Following the last PF feeding test, the rats were maintained on chow alone for a week. Another PF (Oreos)+chow test was performed to verify BEP/BER status. Additionally, a chow-only test was also performed to confirm that there was still no difference in chow intake between groups.

Experiment 5: Effect of diet-induced obesity protocol on BEP/BER status

We wished to test whether BEP/BER status, which is based on a higher intake of PF, was also predictive of DIO proneness or resistance. The classic DIO protocol produces animals that become obese or resist obesity by promoting differential intake of a no-choice 35% fat pellet diet (Research Diets, Diet # D12266B, New Brunswick, NJ, USA) when it is provided continuously for at least 2 weeks.35 Essentially, DIO-prone rats fail to compensate for the additional calories per gram provided by the high-fat diet and continue to eat the same volume of food they ate when only chow was available. DIO-resistant rats adjust their volume of intake downward to compensate for the additional calories consumed. Consequently, obesity prone rats gain more weight than the resistant rats.35 We predicted that if BEPs were also DIO-prone rats, they would uniformly gain a higher percentage of body weight on the high-fat diet than the BER group. Half of the BEP and half of the BER group (N=10/group, weight-matched) were assigned to a traditional DIO protocol.35 The rats were fed ad lib amounts of the high-fat diet for 14 continuous days. It is by this period of time that DIO-prone rats diverge significantly from DIO-resistant rats in body weight gain.35, 36 The middle-most PF consuming group was maintained on chow alone throughout the same 2 weeks. Body weights and 24 h food intakes were recorded daily. The other cohort of BEP and BER rats were used for other studies.

Experiment 6: Effect of continuous access to palatable food+chow on food intake and body weight

The PF+chow choice feeding tests described in Experiment 1 indicated that BEPs ate more PF than BERs not only after a 4 h period but frequently also after 24 h. Hence, we wished to know whether BEPs would gain more weight than BERs if they had daily (vs intermittent) access to the choice diet on which they were classified as BEPs or BERs. After serving in Experiment 5, the same rats were allowed 2 weeks of chow only with a PF+chow test day mid-week to confirm that their BEP/BER status had not changed. They were then placed on a continuous 15-day diet of a choice of Oreo cookies and chow. As in Experiment 5, the middle group was maintained on a chow- only diet throughout the 15 days. Body weights and 24 h food intakes were recorded as in Experiment 5.

Statistical Analyses for all Experiments

Descriptive statistics were used to determine the median kcal scores for each 4 h cookie-feeding test. Cronbach's α was used to verify consistency of high and low PF intake within rats across multiple feeding tests and in DIO-prone vs DIO-resistant group assignment. Between groups differences in chow and PF intake and body weight were determined with analyses of variance (ANOVAs). Bonferroni post hoc tests were conducted when the ‘middle’ BEP/BER group was also entered into the ANOVA. The ANOVA α level was set at 0.05 and all values were expressed as the group mean kcal±s.e.m. for food intake and group mean body weight in grams±s.e.m. The University of Alabama at Birmingham Institutional Animal Care and Use Committee approved all animal procedures.

Results

Experiment 1: Assignment of rats into binge-eating prone or binge-eating resistant groups

The average median kcal value across the feeding tests was 35kcal. Rats assigned BEP or BER status fell into their categories in at least three out of four tests, many falling into one of these groups on four of four tests resulting in a high degree of consistency within rats (Cronbach's α=0.86; results from three sample feeding tests are listed in Table 1). In some of the feeding tests, the BERs consumed more chow than the BEPs (Table 1). Both groups' preference for the PF is evident in that they consumed very little if any chow in the first hour. However, as early as this first hour, the BEPs consume 43.5% more PF than the BERs (Figure 1a) and more than twice as much (55%) by 4 h (Figure 1b). By 24 h, the BERs approach but do not match the BEPs PF intake. Both groups consume equal amounts of chow (Figure 1c). The middle group typically ate equal amounts of chow and an amount of PF intermediate with BER and BEP groups (not shown). Because BEP and BER intake did not differ when only chow was provided on days between the feeding tests, the intermittent increase in intake of the BEPs caused by access to PF did not affect body weight. Therefore, the mean group body weights did not differ throughout the tests. Chow-only tests conducted before and after the choice feeding tests revealed no differences in chow intake between BEPs and BERs (51.6±1.7 vs 50.6±3.9 kcal and 45.6±1.4 vs 46.6±2.4 kcal, respectively, not shown).

Table 1: Kilocalories consumed over the first 4 h in the dark, and cumulative intake over 24 h
Figure 1
Figure 1

Amount of PF consumed at 1 (a), 4 (b) and 24 h of feeding (c) after lights out, used to characterize the binge-eating prone (BEP) from the binge-eating resistant (BER) groups; ***P<0.001, **P<0.01, *P<0.05 BER different from BER. Depicted are results from the fourth PF+chow feeding test.

Experiment 2. Differences between BEP and BER feeding behavior in response to stress

Two hours following footshock, BERs that were stressed were notably hypophagic compared to their non-stressed cohorts (P<0.01). At this time there was no change in the intake of BEPs (Figure 2a). By 4 h (Figure 2b) footshock stress also decreased the characteristic overeating of BEPs (P<0.05) and a food selection effect was observed. The total decrease in food intake of stressed BERs was owed to a decrease in PF intake (P<0.05) whereas the stress-induced suppression in BEPs' intake was owed to a decrease in chow intake (P<0.05). By 24 h, the intake of each stressed group normalized to match that of their non-stressed cohorts.

Figure 2
Figure 2

Amount of chow and PF consumed by stressed and non-stressed binge-eating prone (BEP) and binge-eating resistant (BER) rats in the first 2 h (a) and 4 h of feeding (b); **P<0.01 and *P<0.05 difference in PF intake between BER stress and no-stress; #P<0.05 difference in chow intake between BEP stress and no-stress.

Experiment 3. Differences between BEP and BER feeding behavior in response to hunger

As shown in Figure 3a, hunger produced by overnight chow restriction caused BERs to overeat, mainly chow, in the first hour compared to their sated counterparts (P<0.05). Hunger in the BEPs produced no more eating than in their sated counterparts who expectedly overate compared to sated BERs. Importantly, sated BEPs consumed the same amount of kilocalories as their hungry counterparts only more of the kilocalories came from PF. By 4 h (Figure 3b), previously food restricted BER and BEP rats had still eaten more chow than their sated counterparts (P<0.001). This increased the total intake only of restricted BERs relative to sated BERs (group × energy state interaction on total intake, P<0.02).

Figure 3
Figure 3

Amount of chow and PF consumed by chow-restriction induced hungry vs sated binge-eating prone (BEP) and binge-eating resistant (BER) rats in the first hour (a) and after 4 h of feeding (b); #P<0.05 total and chow intake of hungry vs sated BERs; *P<0.05 difference in total intake of hungry vs sated BERs, ***P<0.001 difference in chow intake between hungry and sated group counterparts.

Experiment 4: Stability of BEP/BER status when using different palatable foods

As shown in Figure 4, the overeating of PF that characterized the BEP rats extended to overeating of other PFs besides Oreo cookies. The greatest intake divergence between groups was observed when the rats were given a non-nutritive high-fat/sweet food that was very similar to the Oreo cookies (the Oreo-like pellet), when given a nutritive non-fat/sweet food (Froot Loops), and when given a non-nutritive/high-fat and nutritive/high-fat food (Crisco and 35% high-fat pellet, respectively). However, the groups did not differ on their intake of candy corn, a non-nutritive/sweet food void of fat, although it was still preferred by both groups over chow. For all foods that were consumed in greater quantity by the BEP group at 4 h, the overeating extended to 24 h with the exception of Crisco. There was no difference in the intake of Crisco or of candy corn between BEPs and BERs at 24 h (82.5±6 vs 73.9±4 and 49.9±3 vs 46.29±2, respectively; not shown). A follow-up Oreo cookie test revealed that the groups remained in their respective initial BEP/BER assignments following exposure to this variety of foods (33.4 kcal vs 24.1 kcal; P<0.01).

Figure 4
Figure 4

Amount of kilocalories of PFs consumed in chronological order, by binge-eating prone (BEP) and binge-eating resistant (BER) rats in the first 4 h of the dark phase. Foods varied in nutritional value and in sugar and fat content, were given with chow and are further described in the text. Oreo-cookie (when given with chow) and chow intake (when given alone) are shown for comparison; BEPs significantly greater intake than BERs at *P<0.05, **P<0.01 and *** P<0.001.

Experiment 5: Effect of diet-induced obesity protocol on BEP/BER status

The body weights of the BEP and BER group did not differ before placement on the continuous high-fat diet (294±5 vs 295.6±5 g, respectively). When the data were analyzed as BEPs vs BERs, the DIO protocol could not discern BEPs from BERs. That is, there was no difference in daily food intake or body weight of BEPs and BERs after 14 days on the high-fat DIO diet (Figure 5a & b). BEPs and BERs ate more than the middle group maintained on chow during the first week only (P<0.01). The BEP and BER groups each gained approximately 15 g (5.2% increase) compared to 5 g (1.6% increase) by the middle chow-maintained group. Inspection of Figure 5a reveals a high degree of within-group variability in weight gain (large s.e.m.s) of the BEP and BER groups compared to the chow-maintained middle group. The large variability within groups was subsequently explained by post-hoc analysis of the data as DIO-prone vs DIO-resistant groups. Each rat was assigned to one of these DIO groups based on individual percent weight gain from the median weight gain score (3.04%). The results revealed that exactly half (N=5) of the BEPs and half (N=5) of the BERs classified as DIO-prone and the other half of each group as DIO-resistant. When classified as such, the groups differed significantly in percent body weight gain, with an 8.3% vs 1.96% increase in body weight for DIO-prone vs DIO-resistant groups, respectively (Figure 5c; P<0.01).

Figure 5
Figure 5

Daily intake (a) and body weights (b) of binge-eating prone (BEP) and binge-eating resistant (BER) rats when placed on a no choice high-fat pellet diet (classic DIO protocol). BEPs and BERs did not differ on these measures. (c) Body weights of BEP and BER rats categorized into DIO prone or resistant based on their percent body weight gain after 14 days of high-fat feeding; **P<0.01, *P<0.05 difference in body weight between DIO-prone vs resistant groups.

Experiment 6: Effect of continuous access to palatable food and chow on BEP/BER status

Figure 6a tracks the groups' body weight throughout the 2 weeks of chow+PF diet. The BEP group weighed more than the chow-only group by the end of the 2 weeks (P<0.001), but there was no statistical difference in body weight or the rate of weight gain between BEPs and BERs. As expected, both groups consumed more kilocalories than the middle group that was maintained on chow alone for most of the 14 days (P<0.01) with the exception of BERs not differing from chow-only rats on days 5, 6, 7 and 14 (ns). BEPs consumed an average of 32% more kilocalories than BERs during the first week (P<0.01) but then reduced their intake such that by the end of the 15 days there was not a statistical difference in intake between BEPs and BERs. Both groups had gained a mean of 10% body weight but at the end BEPs' and BERs' food intake decreased to meet that of chow controls (Figure 6b). Figure 6c and d parse-out the amount of chow and PF consumed (shown together in panel b) to show that the decrease in kilocalories of BEPs was due predominantly to a decrease in PF intake.

Figure 6
Figure 6

(a) Body weights of BEP and binge-eating resistant (BEP) rats during 2 weeks of a continuous choice of chow and PF and of the middle group maintained on chow alone. (b) Corresponding daily food intake of BEPs and BERs on the choice diet compared to a chow-only middle group. BEPs and BERs differed from the chow-only group on all days except on days 5, 6, 7 and 14 (not denoted) when BERs did not differ from the chow-only group; ***P<0.001, *P<0.05 BEP vs BERs. (c: chow) and (d: PF) The breakdown of chow and PF depicted as total intake in (b) is shown.

Discussion

Recognizing that PF plays a very salient role in binge-eating disorders and obesity, we used notable differences in the amount of PF that rats of the same species, age and sex consume to develop a simple but practical model of these disorders. The protocol used to distinguish BEP from BER rats simulates human food-selection patterns that typically consist of nutritious meals and occasional non-nutritive highly palatable snacks and desserts. In summary, BEPs ate consistently more than twice the amount of PF than BERs in a discrete (4 h) interval of time, a criterion for clinical binge-eating.37 These differences in PF intake were observed in two separate squads of rats used here and we predict that the differences will be found in all Sprague–Dawley rats and other outbred strains. Further, we found that BEPs eat as much when sated as when hungry, and when stressed, decrease food intake by eating less nutritious chow but not less PF. Conversely, BERs have a normal hyperphagic response to hunger, are more sensitive to stress-induced hypophagia and this is marked by a suppression in PF but not chow intake (Experiments 2 and 3). With the exception of one PF item, BEP/BER classification held up when other PFs besides Oreo cookies were used (Experiment 4). When the groups are forced to eat a nutritive high-fat diet for 2 weeks, only half of the BEPs and half of the BERs gain significant weight (prove to be diet-induced obese prone; DIO) and the other half are obese resistant (DIR; Experiment 5). However, a daily diet of the non-nutritive PF (cookies) plus chow for the same amount of time causes BEPs to decrease their intake of PF to match that of the BERs and chow only controls (Experiment 6).

Stress is known to trigger overeating in dieters and to trigger binges in those with binge-eating disorders.10, 34, 37, 38 We have reported that rats with a history of restriction also binge on PF when stressed.7, 10, 39 Here we did not expect stress to increase BEPs' and BERs' usual intake of PF because they did not have a history of restriction. We were also not surprised that their intake decreased as stress-induced hypophagia is well documented in laboratory animals.34, 40 However, a novel and surprising finding was that BEPs ate less chow and BERs less PF following stress. The unwillingness to forego PF in BEPs may be mediated by the same mechanisms that drive binge-eaters to seek out PF when stressed or when experiencing negative emotions.41, 42, 43 PF may reduce stress in BEPs. Similar to our BEPs response to footshock stress, Dallman's group found that although rats stressed by physical restraint ate less total calories from a PF and chow choice diet, the proportion of PF consumed increased in the restrained vs unrestrained rats.5 Intake of PF reduced ACTH and corticosterone in these rats, suggesting PF can be used to alleviate adverse effects of stress. Inherent differences in HPA or sympathetic reactivity may predispose the BEPs and not the BERs to turn to PF under stress. BERs may rely on the familiar post-ingestive nutritive effects of chow to deal with stress. A future study of interest will be to assess whether BEP or BER status renders animals with a history of restriction more or less vulnerable to stress-induced binge-eating, respectively. If BERs are protected from stress-induced binge-eating, this model may elucidate the biological mechanisms that protect some individuals from developing binge-eating disorders despite the fact that they diet restrictively and suffer stress. We have preliminary evidence of greater impulsivity, a trait characteristic of binge-eaters,44 in the BEPs vs BERs based on elevated plus maze tests (P<0.05). An extensive battery of similar tests will confirm if indeed BEPs share this other binge-eating trait.

As with stress, the groups also differ in their response to hunger. When energy-deficient, both groups eat more chow than when sated, a behavior reflecting metabolic need.6, 45 However, BEPs consume as much PF when sated as when hungry. This may reflect an altered hedonic drive or higher ‘hedonic set-point’.46 An interesting parallel can be drawn with humans whose increased intake of PF is associated with heightened reward sensitivity.47, 48, 49 Together with the BEPs' reluctance to forsake intake of PF during stress, it will be of interest to explore whether BEPs might not also work harder for the rewarding effects of drugs of abuse compared to the BERs.

Tests using macronutrient-specific diets may reveal whether BEPs and BERs differ in macronutrient preferences. However, such tests would have to control for palatability of the various nutrient-specific diets because the present model is based on differences in amounts of PF consumed, not in preference for PF (both groups preferred PF over chow). Nonetheless, Experiment 4 exposed the groups to PFs of various specific macronutrient content. All of the items tested were preferred over chow by both BEPs and BERs but BEPs ate more of all but one of the PF items compared to BERs when each was given as a choice with chow. This only exception was intake of candy corn, a non-nutritive sweet high-carbohydrate/non-fat food that BEPs and BERs consumed in equal amounts. Failure of BEPs to eat more of this item than BERs cannot be due to decreased palatability of this food because the BERs consumed as much of it as the other PF items, even more than Oreo cookies (Figure 4). The lack of fat in this candy may explain it but BEPs consumed more Froot Loops than BER and this is a very low fat food. Sweetness might be the property driving BEP overeating, but BEPs consumed significantly more of the non-sweet foods (the high-fat pellet and Crisco) than BERs. However, by 24 h, there was no difference in Crisco intake between groups, whereas there was still a difference in the other foods that contained sucrose or a combination of sucrose and fat. Therefore, sweetness or carbohydrate in the form of sucrose cannot be ruled out as important to the BEPs characteristic overeating. Salty junk food was not tested. Cox et al.50 found that the increased caloric intake of obese subjects compared to lean ones was marked not by greater intake of sweets, but of salty/savory foods. Certainly, many junk foods are of the salty variety. Rats respond very favorably to Fonzies, a more salty than sweet food in studies of reward signaling.51 We predict that BEPs would also consume more of these foods compared to BERs. If it is the orosensory, not macronutrient, properties of food that differentiate BEPs from BERs, then BEPs may also be more sensitive to aversive tastes. Negative alliesthesia, where a palatable substance becomes less palatable with repeated ingestion52 may be delayed in BEPs. This would enable BEPs to consume more PF under sated conditions. Follow up studies targeting these possibilities would be clinically valuable because there is no difference between the macronutrient composition of binges and meals in healthy individuals53, 54 and as negative alliesthesia has not been explored in binge-eating studies and only scarcely in obesity studies.55

Another important finding in this study is that BEP/BER classification, or differential amount of PF intake, did not predict DIO proneness or resistance (DIR). In fact, DIO and DIR status was equally represented in each BEP/BER group. This is consistent with humans. Not all with a frequent craving for PF or all that consume PF on a frequent basis develop binge-eating or obesity; just as not all individuals with obesity and/or binge-eating disorders have a ‘sweet-’ or ‘fat-tooth’.17, 56, 57 The BEP rats that gained weight on a high-fat diet (BEP-DIOs) are potentially analogous to obese binge-eating and the BEPs that were obese resistant (BEP-DIRs), analogous to normal weight binge-eating. Binge-eaters resist obesity through compensatory behaviors.37 One way that binge-eaters maintain normal body weight is through reduction of caloric intake.37, 58 Similarly, the BEP-DIRs rats reduce their volume of high-fat intake, thereby reducing total kilocalories consumed, to maintain normal body weight. Although we cannot draw parallels in the motivation underlying a decrease in food intake between BER-DIR rats and restricting humans, shared physiological mechanisms may underlie their apparent ability to go without additional calories, an ability that is clearly compromised in BEP-DIO rats and obese binge-eaters.

Although we found that DIO-prone BEPs and BERs continued to overeat and gain weight on a no-choice high fat diet (the DIO diet), having a choice between chow and Oreo cookies did not produce DIO-obese rats. On this diet, the BEPs (both DIR and DIO BEPs) started compensating for PF hyperphagia by decreasing the amount of PF they consumed so that at the end of 15 days, they matched the PF intake of the BERs and chow controls. This was surprising given that the nutritious and 35% fat DIO diet was similar to the choice diet, which provided nutrition through chow and a high percentage of fat (45%) from the non-nutritive cookies. Although they still gained as much weight as DIO-prone rats on the high-fat die, the different pattern of intake across time between the daily DIO and choice diet predicts that given more time on both diets, DIO-prone BEPs and BERs would have continued on an upward tangent of body weight gain on the high-fat diet, whereas they would not have gained much more weight and possible decreased weight on the choice diet.

Some implications for obese binge-eaters or obese persons with a penchant for PF (analogous to the BEP-DIO group) can be considered from the data. First, normal body weight can be maintained if highly palatable (junk) food is eaten intermittently, not daily, if a low fat baseline diet is adhered to. Secondly, stress may have a tendency to elevate junk food intake in those who already have a tendency to seek out PF. Thirdly, if fatty items are eaten on a daily basis, elimination of fat in a nutritious source (e.g., in meal-typical foods vs in non-nutritive sources) may decrease propensity to gain weight. The data do not advocate eliminating non-nutritive PF (snacks or desserts) because in the choice diet, BEPs had cookies as a choice with chow and began to decrease its intake. There may be something about parsing out fat content from nutritive meals that results in lowered daily caloric intake. Perhaps humans (and rats) can eat only so much non-nutritive (‘junk’) PF but the ceiling on intake for fats in nutritive sources may be higher. Interestingly, Green et al.59 found that among obese women, the total amount of calories consumed in a day was significantly higher when high-fat foods were eaten as a meal, but not as a snack. They suspect that this may be partly owing to the fact that meals involve a larger ‘eating episode’ than snacks. Fourthly, another implication from the data is that if junk food loses its novelty through daily, vs occasional consumption, those with a high drive or maladaptive craving for PF, as occurs in binge-eating, may gradually eat less of it. This implies that novelty may underlie part of the BEPs hyperphagia of PF. Mechanistically, accumbens dopamine may be stimulated at higher levels in BEPs than BERs when exposed to PF intermittently. However, with continuous access to PF, dopamine release should adaptively regulate in a negative manner to normalize responding to PF, without affecting the palatable nature of the PF.60 This would explain why BEPs normalized their intake of PF when they had it continuously but also why BEPs and BERs still continued to prefer it to chow. In binge-eaters, regarding PF as forbidden and restricting access to it may only serve to increase consumption of this food when it does become available. Allowing reasonable daily access to it may actually reduce desire for highly PF. A caveat, however, is that the rats in this model were not calorie-restricted nor had a history of caloric restriction, whereas some human binge-eaters insist on restrictive dieting. This may alter the dynamics of frequent PF intake and even worsen the condition by triggering binges as we have seen it do in rats that were repeatedly restricted.6 A fifth implication is a caveat directed to animal researchers: amount of chow intake in rats does not predict how much PF rats will eat. Because we confirmed that PF over- or under-eating is stable, failure to control for these differences can compromise the veracity of experimental results using PF.

In conclusion, this study offers a simple, low-labor and reliable animal model of lean and obese binge-eating, and of obesity with and without binge-eating. It can be used to begin deciphering the neural and endocrine factors that mediate these clinical conditions and to understand the substrates behind a high vs low drive for PF. Candidate targets include central peptide YY, opioid-receptor, dopamine and serotonin, as substrates for motivated feeding, reward and mood regulation.10, 61, 62, 63, 64 These are only a few targets and do not include others such as the melanocortin-4-receptor, galanin, NPY and other peptides implicated in specific macronutrient selection, should such preferences be involved in the feeding differences of BEPs and BERs. Importantly, the individual differences approach used in this model of binge-eating may reveal genetic vulnerabilities to bulimia, binge-eating disorder and binge-purge anorexia nervosa. Besides the ‘BEP’ characteristics that parallel these disorders including increased intake of PF under sated conditions, selection of PF over less PF after stress, and ability in some BEPs to resist overweight despite a tendency to binge-eat on PF, another parallel may be reward sensitivity which is also implicated to characterize individuals with eating disorders.32, 65, 66, 67

Our food-hedonic environment is not expected to change, it would be valuable to know how the BEP-DIR rats are able to overindulge in PF food but still maintain normal caloric intake to keep them from gaining weight. This describes the eating behavior of some of us described as ‘lucky’ by those battling overweight and/or binge-eating. Knowing that luck has nothing to do with it, we can use this animal model to identify behavioral and physiological targets to aid those less lucky of us (>65% of Americans).

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Acknowledgements

This work was funded by a NIH grant DK066007, a UAB Support for Development and Application of Research Using Animal Models (SDARAM), and NIH CNRU grant P30DK056336.

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    • M M Boggiano

    Former name MM Hagan.

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  1. Department of Psychology, Behavioral Neuroscience Division, University of Alabama at Birmingham, Birmingham, AL, USA

    • M M Boggiano
    • , A I Artiga
    • , C E Pritchett
    • , P C Chandler-Laney
    • , M L Smith
    •  & A J Eldridge

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https://doi.org/10.1038/sj.ijo.0803614

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