Effect of naltrexone on food intake and body weight in Syrian hamsters depends on metabolic status

Opioids are a family of neuropeptides involved in the control of food intake and regulation of body weight. In general, nonselective opioid antagonists have inhibited food intake in a variety of paradigms in rodent species. Syrian hamsters may be an exception to the general findings. In a previous report, we showed that systemic administration of an opioid antagonist, naltrexone, for 2 days increased body weight in female Syrian hamsters. To confirm the extent of these finding we designed the present experiment testing the effect of a chronic 6-day infusion of naltrexone on food intake, water intake, and body weight in freely feeding male hamsters. In addition, we examined the effect of acute administration of naltrexone on food intake in both ad-libitum-fed and food-deprived hamsters. We found that chronic systemic administration of naltrexone caused a significant increase in food intake and body weight. Second, acute administration of naltrexone decreased food intake after a 48-h fast but had no effect in ad-libitum-fed hamsters. Water consumption was not altered in any experimental paradigm. Our results suggest that opioid circuits in Syrian hamsters may function tonically to suppress food intake and body weight when Syrian hamsters are in positive energy balance. Paradoxically, opioids may enhance food intake after a sustained fast.     

Overcompensation of food intake following brief periods of food restriction

Four adult female Sprague-Dawley rats, maintained on an ad lib feeding schedule were deprived for either 0, 0.5, 1, 2, 4, 6, or 8 hours during the dark phase of the day-night cycle. It was found that the latency to initiate the first meal following the deprivation was independent of the previous deprivation interval. The animals were found to overcompensate for the periods without food by eating a large initial meal that increased proportionately in size with the duration of food restriction. Furthermore, the animals continued to overeat throughout the day. This deprivation-induced overeating by the animals resulted in an overcompensation in total food consumption that was 21–56% greater than on control days. The role of food intake as a regulator of body weight is discussed.     

Evidence for the role of insulin-like growth factor II (IGF-II) in the control of food intake

Highly purified insulin-like growth factors I and II and insulin (100 ng peptide/animal) were injected intracerebroventricularly in rats and the effect on 24 hour food consumption examined. IGF-II injections resulted in a 21% decrease in food intake and 4% body weight loss over the 24 hour period following peptide administration whereas IGF-I and insulin had no effect on either parameter. Increasing the amount of IGF-II injected also increased these responses with depressions of 22, 33 and 44% occurring in rats given 33, 100 and 300 ng IGF-II respectively. In addition, tissue concentrations of IGF-II were detected and found to be differentially distributed, via radioimmunoassay, in specific regions of the brain implicated in the regulation of food intake. IGF-I was not found in these same tissue punches despite radioimmunoassay sensitivity of 6 pg.     

Food intake of rats administered with glycerol

The effect of glycerol on rats food intake was determined when it was administered either via bolus gastric intubation, or by a continuous 24 hr infusion into the aorta. Both of these treatments resulted in a suppression of the 24 hr food consumption to an extent which was greater than that accounted for by the caloric value of the administered metabolite. Gastric loading with urea solutions equiosmotic to glycerol or with glucose solutions equicaloric to glycerol were less effective than glycerol in reducing the 24 hr food intake. The time course effect on food intake varied between gastric loading with glycerol and with equicaloric glucose solutions, with the former usually exerting a more delayed and longer lasting effect. Continuous intraaortal infusions of glycerol were more effective than glucose solutions in suppressing 24 hr food intake even though the latter had twice the caloric value of the former. Our data suggest that the action of glycerol on food intake is not mediated through its conversion to glucose. The possibility that glycerol may participate in a lipostatic control mechanism of food intake is discussed.     

Variety in the diet enhances intake in a meal and contributes to the development of obesity in the rat

Male and female rats were given three palatable, high energy foods either simultaneously or in succession during three 40 min courses. Both simultaneous and successive variety enhanced energy intake compared to the intake of single palatable foods, which was itself enhanced compared to the intake of chow. Rats deprived of food for 24 hr showed a compensatory increase in chow intake (84%) but only a 20% increase in intake in the single palatable food conditions, and no increase in the variety conditions. Male and female rats showed a similar response to variety and deprivation. The effect of variety on body weight was also examined in rats offered either chow, or chow and one palatable food, or chow and three palatable foods in succession (changed every 12 hr) or simultaneously, for seven weeks. All rats offered the palatable foods were hyperphagic compared to chow-fed controls. Rats given the simultaneous but not the successive variety diet were more hyperphagic than the other palatable food groups and showed significantly greater body weight and fat gains. The availability of a variety of foods is an important factor in the amount eaten in the meal and in the etiology of obesity.     

Insulin infusion during a nocturnal fast suppresses the subsequent day-time intake

Much recent evidence suggests a dual and opposite action of insulin on food intake and body weight. Peripherally administered, long acting insulin stimulates weight gain and food intake. On the contrary intracerebroventricularly infused insulin decreases food intake and body weight. It has been suggested that the shift from the nocturnal hyperinsulinism and hyperphagia to the day-time hypoinsulinism and hypophagia depended on the action of insulin on the brain during the night. It has also been hypothesized that the absence of nocturnal hyperinsulinism due to fasting was partly responsible for the hyperphagia observed during the subsequent day-time. In the present experiment, insulin was infused intravenously at various low doses (0.01, 0.025, 0.05 U/hr) during a nocturnal fast. Its effects on the following diurnal free food intake were investigated. It was shown that the experimentally elevated plasma insulin induced a dose-dependent reduction in the day-time feeding response. It was concluded that this reduction is due to the chronic action on the brain of the high plasma insulin level induced by the infusion during the nocturnal fast.     

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.     

Effects of early cold adaptation on food efficiency and dietary-induced thermogenesis in the adult rat

The food intakes of male and female rats (Harvard strain) adapted to cold (5°C) starting at weaning were studied in the cold and during reacclimation to 25°C. Following 24 hr food deprivation, the male rats regained the weight they had lost without making up for the food they had missed (increased food efficiency), while the female rats ate 75% more food than they had missed in regaining their body weights (decreased food efficiency), independent of the temperature at which the animals were housed. On a high fat diet, both cold groups gained less weight than did the two control groups. However, each female group gained significantly less weight than its same temperature male group. Dietary-induced thermogenesis was significantly enhanced in male cold adapted rats 3 months after reacclimation to the zone of thermal neutrality but not in cold adapted female rats. Sex and strain differences are discussed. These data indicate that early chronic cold exposure results in both immediate and long-term changes in food efficiency and metabolism in adult rats, but the effects vary with the sex of the animal.     

Absence of post-fast food compensation in the golden hamster (Mesocricetus auratus).

Ad lib food intakes and body weights were measured for hamsters fed one of 4 different diets. Animals were then placed on an intermittent starvation (IS) schedule in which food was available ad lib on alternate days only. Hamsters of both sexes showed little or no post-fast food compensation, i.e., after 24 hr of food deprivation their daily food intake was no greater than their daily intake during baseline testing. These animals lost a large percentage of their initial body weight and many of them died. Other hamsters restricted daily to half-day feeding periods that nearly coincided with the light (L) or dark (D) phases of the illumination cycle also failed to show food compensation; they generally ate no more during D- or L-periods that followed a half day of food deprivation than during D- or L-periods that succeeded a half day of ad lib feeding. These animals lost substantial portions of their initial body weight and many died. Hamsters refed after a 96-hr fast and an 18% loss in body weight also did not increase their food intake substantially above baseline values. In each of these experiments substantial portions of the body weight lost during starvation were not regained during extended ad lib refeeding regimens. These findings contrast strikingly with the behavior of rats tested concurrently; rats showed a dramatic post-fast hyperphagia, rapid recovery of body weight lost during starvation, and a reversal of the normal nocturnal feeding pattern when refeeding began during L-periods. Hamsters' nocturnal rhythms of eating and drinking were remarkably stable in the face of all the experimental manipulations. However, hamsters, as well as rats, were quite effective in compensating for changes in diet density; a 1:1 dilution of a liquid diet produced a prompt doubling in the volume of diet ingested. Impressive but less complete compensation was recorded when solid diets were diluted with inert substances (kaolin, cellulose). Hoarding and perhaps hibernation rather than compensation may have evolved as adaptations to periods of food scarcity. Noncompensation may be related to hamsters' nonresponsiveness to some signal of energy depletion. The possibility of lipogenesis being a rate-limiting step is considered. The desirability of adequate field data as a prerequisite to laboratory analysis of feeding behavior is emphasized.     

Hyperactivity and obesity: The interaction of social isolation and cafeteria feeding

Rats were reared in social isolation or in social groups of 4 or 5 rats per cage from weaning and were fed either a lab chow diet or a diet of 4 palatable foods (cafeteria diet), in addition to the lab chow. The hyperactivity of isolation-reared rats appears to be a reactivity to novel environmental stimuli, since it was seen only in the 0.5 hr tests and not in the near 24 hr test. It was found that hyperactivity and increased body weight can develop within as few as 7 to 10 days in rats reared in isolation from weaning. Cafeteria feeding enhanced activity in isolation-reared rats, but suppressed it in group-reared rats. Isolation-reared rats fed a cafeteria diet had strong, stable preferences for their most preferred food over the 25 days of measurement. Rats reared in isolation had significantly different food preferences, as compared with rats reared in groups. Cafeteria fed rats had a significantly greater calorie intake and body weight than rats fed lab chow. On analysis, cafeteria fed rats had significantly greater carcass energy and an increased amount of parametrial white adipose tissue as compared with rats fed only lab chow. The interscapular brown adipose tissue (IBAT) weights of cafeteria fed rats were also greater. However, as there was no difference between the cafeteria and chow fed rats in the total amount of protein in the IBAT, it was concluded that the increased weight of the IBAT did not reflect a genuine hypertrophy of the tissue.     

Repeated hypothalamic stimulation with neuropeptide Y increases daily carbohydrate and fat intake and body weight gain in female rats

Neuropeptide Y (NPY), repeatedly injected in the hypothalamic paraventricular nucleus (PVN), produces dramatic obesity and overeating in female rats maintained on a single nutritionally complete diet. In the present study, we investigated whether these effects could also be obtained in animals with a choice of three pure macronutrients: protein, carbohydrate, and fat. Female rats with indwelling PVN cannulas were injected with NPY (235 pmol) or its saline vehicle every 8 hr for 6 days. A third group was left undisturbed. Consumption of each macronutrient and body weight were measured every 24 hr for 6 days preinjection, 6 days during injections, and 21 days after the injections were terminated. Relative to vehicle or preinjection rates of body weight gain (approximately 1.5 g/day), NPY dramatically enhanced weight gain to a rate of 9.3 g/day and more than doubled total daily food intake. This augmentation was accounted for by increases in carbohydrate intake (+26.4 kcal/day) and fat intake (+48.5 kcal/day), with no significant potentiation of protein consumption. When the NPY injections were terminated, body weight and macronutrient intake returned to control levels within 1 or 2 weeks. These findings are consistent with a role for NPY in hypothalamic mechanisms of macronutrient intake and body weight regulation and suggest that disturbances in brain NPY may contribute to the development of eating and weight disorders.     

Consumption of a high-fat diet induces central insulin resistance independent of adiposity

Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HF, low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of LF and chow rats but had no effect on HF rats in either the chronic or the acute experiment. Rats chronically pair-fed the HF diet to match the caloric intake of LF rats, and with body weights and adiposity levels comparable to those of LF rats, were also unresponsive to i3vt insulin when returned to ad libitum food whereas rats pair-fed the LF diet had reduced food intake and body weight when administered i3vt insulin. Insulin's inability to reduce food intake in the presence of the high-fat diet was associated with a reduced ability of insulin to activate its signaling cascade, as measured by pAKT. Finally, i3vt administration of insulin increased hypothalamic expression of POMC mRNA in the LF- but not the HF-fed rats. We conclude that consumption of a HF diet leads to central insulin resistance following short exposure to the diet, and as demonstrated by reductions in insulin signaling and insulin-induced hypothalamic expression of POMC mRNA.     

Defense of a lowered weight maintenance level by lateral hypothamically lesioned rats: Evidence from a restriction-refeeding regimen

Male rats maintained their body weight at approximately 85% that of sham-lesioned controls following lesions of the lateral hypothalamus (LH). One month following surgery, the food intake of half the LH-lesioned animals was restricted until their body weight had declined to 80% that of nonrestricted LH animals. Half the sham-lesioned animals were similarly restricted until their body weight fell to 80% that of nonrestricted control animals. When returned to an ad lib feeding schedule, both restricted groups were initially hyperphagic and quickly restored their body weights to the level of the nonrestricted group from which they were originally selected. In doing so, the LH animals increased their food intake by the same amount and took the same number of days to restore their weight to control levels as the sham-lesioned animals. These observations provide further evidence of the vigor and effectiveness with which LH animals defend their reduced level of maintained body weight.     

Effects of chronic intrahypothalamic infusion of insulin on food intake and diurnal meal patterning in the rat

In Experiment 1, rats were chronically infused with insulin (2.7, 27, or 270 ng/hr) or 0.9% saline into the ventromedial (VMH), medial perifornical (PF), or lateral (LH) hypothalamus. VMH infusions of insulin caused a significant, dose-dependent decrease in food intake and body weight; PF infusion of insulin was less effective, but significant; whereas LH infusions of insulin were ineffective. In Experiment 2, rats were chronically infused with insulin (0.54 ng/hr) or 0.9% saline into the VMH, paraventricular (PVN), or posterior (PN) hypothalamic nucleus. Subjects that received VMH or PN infusions of insulin failed to regain weight lost as a result of surgery even 2 weeks after infusion; subjects that received PVN infusions of insulin regained their preoperative weights faster than did controls. All of the groups that received insulin significantly increased their daytime food intake during the infusion period and decreased their night food intake slightly; 24-hr food intake remained unchanged.     

Effects of selective estrogen receptor agonists on food intake and body weight gain in rats

Ovariectomized (OVX) rats eat more and gain weight more rapidly than sham-operated (SO) rats and estradiol (E(2)) treatment attenuates food intake and body weight gain in OVX rats. Studies were designed to test the hypothesis that the alpha subtype of the estrogen receptor (ERalpha) mediates the attenuating effects of E(2) on food intake and body weight gain while the beta subtype (ERbeta) mediates opposing actions that lead to increased food intake and body weight gain. Female rats were SO or OVX and treated daily with vehicle (dimethylsulfoxide, DMSO) or E(2) (10 microg/day), or the ERalpha-selective agonist, 4,4',4'-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, 0.5 mg/day), or the ERbeta-selective agonist, 2,3-bis(4-hyroxyphenyl)-propionitrile (DPN, 0.5 mg/day) for 14 days. Total food intake was significantly reduced by E(2) and PPT, but not DPN. Total body weight gain was significantly increased in OVX rats compared to SO rats and treatment with E(2) or PPT, but not DPN, significantly decreased total body weight gain to levels that were not significantly different from SO rats. A dose-response study of PPT indicated that at 0.25 mg/day, PPT significantly reduced total 21-day food intake and body weight gain and, at 0.13 and 0.06 mg/day, PPT significantly reduced total body weight gain compared to OVX rats without significantly reducing total food intake. A dose-response study of DPN indicated that none of the three doses of DPN significantly altered total 21-day food intake or total body weight gain. These results suggest ERalpha mediates the attenuating effects of estrogens on food intake and body weight gain while ERbeta has no effect on these variables.     

Alleviation in the rat of a GABA-induced reduction in food intake and growth

Cold exposure and diet dilution which stimulate food intake of normal rats lessened depressions of food intake and growth induced by dietary GABA. During a 3-day adaptation to the cold, rats fed a diet containing 4.5% GABA lost weight; thereafter, food intake and growth rate differed little from those of cold control rats and were usually greater than those of normal rats fed GABA. Hepatic GABA-aminotransferase activity of cold-exposed rats fed the GABA diet increased to about twice that of normal control rats. Rats fed a control diet diluted by half with cellulose ate 50% more of this diet than of the undiluted diet but gained only 20% less weight. Rats ate twice as much of a diluted, 9% GABA diet as of an undiluted, 4.5% GABA diet (thus doubling their GABA intake) and gained three times as much weight. A novel food (condensed milk) barely lessened the adverse responses to GABA. These results show that conditions requiring rats to increase their food intake in order to maintain body weight can also increase their acceptance of a diet high in GABA.     

Effect of crowding on some physiological and behavioral variables in adult male rats

The effect of two population densities on body weight gain, food and water intake and the weight of some organs and glands was studied in adult male rats. Behavioral reactivity to open field was also assessed. Crowded rats (10 animals per cage) showed lower body weight gain than control rats (3 per cage) throughout all the experimental period. Crowding decreased food intake and increased water intake. Any effect of crowding on the weight of thymus, liver and endocrine glands (except testes) was found. Open field defecation and activity were the same in control and crowded rats. Discrepancies from earlier works could likely be due to methodological differences and these are discussed in the text.     

Intracerebroventricular infusions of rat satietin into rats does not produce conditioned taste aversion

In a previous study we found that while human satietin (h-SAT) suppressed the food intake of rats it was also aversive to them. In the present study rat satietin (r-SAT) was tested for aversiveness in rats fitted with chronic third ventricle (ICV) cannulas. The rats were then given access to water for 1-hr/day and food ad lib for ten days. Fluid intake, food intake during fluid access and 24-hr total food consumption were recorded. The rats were then ICV infused with saline and 30 min later half of the animals given access to banana flavored water (Group 1) while the remainder were presented with almond flavored water (Group 2). The next day Group 1 was infused with saline and Group 2 with 100 micrograms/rat of r-SAT. Thirty minutes later the flavors presented to the rats were the reverse of the previous day. Satietin significantly reduced food intake during fluid access and for 24 hours. Thereafter, fluid and food ingestion of the groups was normal and similar. Thus no rebound feeding occurred in the r-SAT treated group. Two days after r-SAT or saline the rats were given a two-bottle choice test. Both groups displaced equal preference for the flavors, therefore r-SAT produced no taste aversion. The r-SAT treated rats lost more body weight than saline treated animals the first day after treatment. This difference increased the next day and remained significant for seven days post infusion, whereas, food consumption did not differ between the groups after the first day. The data indicate the food intake suppression in rats produced by r-SAT is not due to the compound being aversive.     

Food, water and saccharin solution intake in trats with posterior striatal lesions

Albino rats either received bilateral electrolytic lesions in the posterior striatum or were subjected to a control operation. Striatal damage was not found to influence food intake, water intake, the differential consumption of a saccharin solution and water, or body weight, the data being expressed in relation to preoperative body weight. An interpretation of the results is presented, and their bearing on some previously reported findings is noted.