Effect of dietary macronutrients on food intake, body weight, and tail width in the marsupial S. crassicaudata

The role of dietary fat, as opposed to total energy intake, in the etiology of obesity is controversial. The aim of this study was to determine the effect of macronutrient content, specifically changes in dietary fat on body weight, fat stores, and food intake in S. crassicaudata, a marsupial that stores about 25% of total body fat in its tail. Female animals were divided into three groups (n = 7-9) matched for food intake per gram of body weight. Each group of animals was fed, ad lib an isocaloric diet (1.01 kcal/g), which contained either 10, 20, or 40% of calories from fat. Body weight, food intake, and tail width (an index of body fat stores) were measured daily. Over 21 days, cumulative energy intake was less (p = 0.026) in the 40% fat group compared to the 10% fat group. Despite the differences in food intake, body weight in each group remained stable throughout the study, so that at day 21 there were no differences in the body weights between the three groups. In contrast, tail width increased in the animals who received the 40% fat diet compared to either the 10% (p = 0.016) or 20% (p = 0.001) fat intake groups, whereas there was no significant change in tail width in either of these two groups. These observations indicate that macronutrient composition has a role, independent of total calories in the regulation of food intake and body fat stores, specifically that dietary fat promotes adiposity, independent of total caloric intake.     

MSG intake suppresses weight gain, fat deposition, and plasma leptin levels in male Sprague-Dawley rats

Monosodium l-glutamate (MSG), an umami taste substance, may be a key molecule coupled to a food intake signaling pathway, possibly mediated through a specific l-glutamate (GLU) sensing mechanism in the gastrointestinal tract. Here we investigated the effect of the spontaneous ingestion of a 1% MSG solution and water on food intake and body weight in male Sprague-Dawley rats fed diets of varying caloric density, fat and carbohydrate contents. Fat mass and lean mass in the abdomen, blood pressure, and several blood metabolic markers were also measured. Rats given free access to MSG and water showed a high preference (93-97%) for the MSG solution, regardless of the diet they consumed. Rats ingesting MSG had a significantly smaller weight gain, reduced abdominal fat mass, and lower plasma leptin levels, compared to rats ingesting water alone. Naso-anal length, lean mass, food and energy intakes, blood pressure, blood glucose, and plasma levels of insulin, triglyceride, total cholesterol, albumin, and GLU were not influenced by the ingestion of the MSG solution. These same effects were observed in a study of adult rats. Together, these results suggest that MSG ingestion reduces weight gain, body fat mass, and plasma leptin levels. Moreover, these changes are likely to be mediated by increased energy expenditure, not reduced energy intake or delayed development. Conceivably, these effects of MSG might be mediated via gut GLU receptors functionally linked to afferent branches of the vagus nerve in the gut, or the afferent sensory nerves in the oral cavity.     

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.     

Paradoxical stimulation of food intake by larger loads of glucose,fructose and mannose: Evidence for a positive feedback effect

The phenomenon of paradoxical stimulation of food intake by larger alimentary loads of isotonic glucose was studied with regard to a variety of experimental and nutritional conditions. Thus, paradoxical feeding response was induced not only by the infusions of glucose but also of the other insulinogenic sugars—fructose and mannose. Stimulation of food intake was further observed following the administration of larger volumes of isotonic glucose solutions via the duodenal and intraperitoneal infusion routes in free feeding as well as in 12 hr food-deprived animals. This paradoxical alimentary response was not eliminated or reduced by repeating these infusions daily over a longer period of time; in fact, food in the first postinfusions hour and, unexpectedly, also the total daily food intakes, showed a gradually increasing trend with daily repetitions. Drinking of isotonic glucose for 1 hr in 12 hr water-deprived animals did not suppress the subsequent intake of regular food despite the substantial amount of glucose drunk (94.1 ml vs 76.5 ml of water in controls during the same time period). The conbination of glucose drinking with subsequent food intake resulted in a significant caloric imbalance during the first hour which was not fully compensated within the 24 hr. These findings indicate that larger loads of insulinogenic sugar loads are capable of triggering an antiregulatory positive feedback alimentary response which can induce caloric imbalance and thus adversely affects the short-term maintenance of energy balance.     

Effects of dietary caloric density on feeding behavior in Mongolian gerbils (Meriones unguiculatus)

Total daily energy intake, water intake, body weight, and meal patterns were studied in Mongolian gerbils as a function of dietary caloric density. On diets ranging in caloric density from 2.25 kcal/g to 6.09 kcal/g, gerbils consumed an average of 40 kcal per 100 g of body weight per day. In comparison to gerbils fed ground Purina Laboratory Chow (4.2 kcal/g), gerbils presented with diets diluted with nonutritive cellulose increased food intake in proportion to the percentage of cellulose added. Gerbils given diets in which the caloric density was increased by the addition of fat, decreased food intake as a direct function of the added fat. Water intake was increased on the calorically diluted diets, and decreased on the concentrated diets. Body weight did not vary as a function of dietary conditions. On a standard pelleted diet (Noyes), gerbils ate approximately 18 meals a day. Average meal size was 0.4 g. When presented with calorically diluted pellets, gerbils maintained daily energy intake by increasing both meal frequency and meal size. There were no differences in food intake, meal frequency or meal size between the light and dark portions of the 24-hr cycle.     

Effects of glucose, aminoacid or lipid infusion on dietary self-selection in the rat]

Rats with an intracardiac chronic catheter were offered dietary self-selection between glucids, proteins and lipids intakes. They are infused continuously with 0.9% NaCl except on the test day with glucose, amino acids or lipids. Parenteral load is about 25% of the daily total food intake. With glucose infusion a selective decrease in glucids intake is observed of about 80% of the caloric glucose load. Aminoacidemic and lipidic infusions lead not only to decrease respectively in proteins and lipids intakes, but also in glucids intakes. So, in this case, total caloric intake decreased more than caloric load. Results are discussed in the hypothesis of existence of a hepatic chemosensibility.     

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

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

The comparative effects of abrupt vs. stepwise discontinuation of TPN in rats.

The comparative effects of discontinuing total parenteral nutrition (TPN: caloric ratio of glucose:fat:amino acid = 50:30:20) abruptly or in a stepwise manner on spontaneous food intake were investigated in two studies. Study 1: In 16 rats, TPN was given for 4 days, then stopped abruptly in eight rats. In the other eight rats, TPN was tapered; they received TPN at 75%, 50%, and 25% of their mean daily energy requirements per day for 3 consecutive days, and then switched to normal saline. Total parenteral nutrition induced a significant 60% reduction in spontaneous food intake (SFI) in both groups during the first TPN day. After 4 days of TPN, an 80% decrease in SFI had occurred in both groups. Resumption of SFI was significantly sooner in the abruptly-stopping group than in the stepwise-stopping group. But, in the latter group, there was a significantly greater cumulative caloric intake during the entire study. Study 2: In 32 rats, TPN providing either 100%, 50%, or 25% of their mean daily caloric requirements was given to three groups each of eight rats, for 3 days, then abruptly changed to normal saline; control rats received normal saline throughout. The TPN-induced decrease in SFI was proportional to the caloric density of the solution infused. Three days of 100%, 50%, or 25% TPN infusion led to an approximate 85%, 60%, or 35% decrease in SFI, respectively. Spontaneous food intake recovery was independent of the caloric density of TPN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary hyperphagia in rats: role of fat, carbohydrate, and energy content

Dietary energy, fat and carbohydrate content were varied to determine the nutritional factors responsible for hyperphagia induced by feeding rats high-fat diets. In the first experiment, rats were fed isoenergetic high-fat or high-carbohydrate diets for 2 weeks. Weight gain and energy intake were lower in rats given the high-fat diet. When some of the rats were switched to a diet that was high in fat, carbohydrate and energy, gram food intake was initially unchanged, resulting in a substantial increase in energy intake and weight gain. Energy intake gradually declined over the 4 weeks following the switch to the high-energy diet. In the second experiment, rats were fed high-fat diets that were either high or low in carbohydrate content and either high or low in energy content (kcal/g). Rats fed a high-fat diet that was high in energy and carbohydrate ate the most energy and gained the most body weight and carcass fat. In the third experiment, rats were fed high-carbohydrate diets varying in fat and cellulose content. Energy intake and body weight gain varied directly as a function of caloric density regardless of the fat or cellulose content of the diets. It is concluded that hyperphagia induced by feeding high-fat diets is not due to the high dietary fat content alone. Rather, high levels of fat, carbohydrate, and energy interact to produce overeating and obesity in rats fed high-fat diets.     

Effects of equicaloric loads of protein, fat, and carbohydrate on food intake in the rat and man.

Two experiments were conducted, one in the rat and one in man, to ascertain the effects of equicaloric loads of protein, fat, carbohydrate, and a mixture of these, on subsequent food intake. Additionally, non-caloric loads were given. In the rat, loads were administered intragastrically, and ad lib food intake was measured after various intervals. Corn-oil loads suppressed food intake less than other equicaloric loads. This suggests that calorie-for-calorie, fat does not suppress intake as much as protein or carbohydrate. Sucrose loads suppressed food intake the most after 1$\text{1}\text{2}$ hr. Mixture loads had an effect equal to the average of its components after 24–72 hr. In man, loads were given orally after a 13-hr fast. Differences between loads were minimized by suppressing olfaction with noseclips, and taste with topical anesthesia of the mouth. Consumption of test-meal presented 70 min later was measured. Also, various ratings of appetite were made. No differences were found between intakes or ratings after individual loads. But collectively, caloric loads suppressed food intake more than non-caloric loads.     

Food intake and behavioral caloric compensation after protein repletion in the rat

The food intake response of rats to intragastrically infused or orally consumed protein was characterized and compared to the response to similarly administered carbohydrate. In Experiment 1, protein hydrolysate loads administered at the beginning of the dark phase via chronic intragastric cannulae led to rapid (complete within 3–4 hr), dose-related suppressions of food intake in comparison to sham loads or to urea loads controlling for volume, concentration and pH. The suppression remained evident in cumulative intake records through 24 hr and represented a greater than caloric compensation for the amount of metabolizeable energy delivered (1.38 and 1.12 kcal/kcal in Experiments 1a and 1b, respectively). In Experiment 2, protein hydrolysate loaded by gavage suppressed food intake significantly more than isocaloric glucose loads (1.32 vs 0.81 kcal/kcal after 24 hr). Water intake in both experiments was elevated by protein loads, although this occurred after the food intake suppression. Differential satiety responses to protein and carbohydrate repletion were shown in Experiment 3 to extend to orally consumed, naturally occurring macronutrients—casein vs starch and disaccharide diets. These data suggest that satiety in the rat is not solely graded with respect to the energy delivered by the preceding meal but rather that repletion with different macronutrients leads to quantitatively (or perhaps qualitatively) different satieties.     

Regulation of feeding behavior in the prepubertal female rat.

Responses to challenges of long-term regulation of feeding behavior were compared between adult and weanling female rats. Adulteration of a high fat diet with NaCl caused both adult and weanling rats to reduce their food intake, but neither group refused to eat. Food deprivation for 24 hr was followed by an increase in feeding for both adult and weanling animals during a period when food intake is normally very low. Continued limited food access to 2 hr during the light period was compensated for by an increase in the normal food intake for this period for both adult and young female rats. It was observed that both adult and weanling rats showed a marked preference for the more dilute glucose solution when given a choice. In addition, both groups maintained a constant caloric intake during presentation of the glucose solutions by adjusting their intake of a solid food source. In each challenge of long-term regulation of feeding behavior, the response of weanling animals was as good or superior to that shown by adults. It is concluded that weanling female rats regulate their feeding just as adults to maintain long-term energy balance. It was also observed that bilateral lesions placed in the ventromedial hypothalamus (VMH) at 21 days of age resulted in reduced daily food intake and retarded body weight gain. Furthermore, young rats with VMH lesions failed to respond to 24 hr of food deprivation or limited food access. These data suggest an important role for the VMH in the long-term regulation of feeding in young rats.     

Caloric imbalance induced by failure of food intake to compensate for caloric supply provided by diurnal or nocturnal drinking of isotonic glucose

Free-feeding rabbits allowed to drink isotonic glucose failed to reduce food intake sufficiently to compensate for the extra caloric supply. This resulted in a considerable caloric imbalance which was not compensated during the diurnal or nocturnal periods when the animals were drinking glucose. Reductions of food intake were smaller or even paradoxically reversed following repeated exposures to glucose despite the fact that the intake of fluids was more doubled. Equi-osmotic equi-volumic saccharin solutions drank voluntarily or infused into the duodenum did not produce paradoxical feeding response. Blockade of insulin-dependent lipogenesis by Atromid S prevented the paradoxical stimulation of food intake by larger duodenal loads of glucose.     

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

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

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.     

High-intensity sweeteners and energy balance

Recent epidemiological evidence points to a link between a variety of negative health outcomes (e.g. metabolic syndrome, diabetes and cardiovascular disease) and the consumption of both calorically sweetened beverages and beverages sweetened with high-intensity, non-caloric sweeteners. Research on the possibility that non-nutritive sweeteners promote food intake, body weight gain, and metabolic disorders has been hindered by the lack of a physiologically-relevant model that describes the mechanistic basis for these outcomes. We have suggested that based on Pavlovian conditioning principles, consumption of non-nutritive sweeteners could result in sweet tastes no longer serving as consistent predictors of nutritive postingestive consequences. This dissociation between the sweet taste cues and the caloric consequences could lead to a decrease in the ability of sweet tastes to evoke physiological responses that serve to regulate energy balance. Using a rodent model, we have found that intake of foods or fluids containing non-nutritive sweeteners was accompanied by increased food intake, body weight gain, accumulation of body fat, and weaker caloric compensation, compared to consumption of foods and fluids containing glucose. Our research also provided evidence consistent with the hypothesis that these effects of consuming saccharin may be associated with a decrement in the ability of sweet taste to evoke thermic responses, and perhaps other physiological, cephalic phase, reflexes that are thought to help maintain energy balance.     

Influence of early dietary experience on energy regulation in rats

The environmental mechanisms that have contributed to the rapid increases in overweight and obesity in the US over the past 25-30 years have yet to be fully specified. One hypothesis that has been forwarded is that increased consumption of calories in liquid form may be a contributing factor, since some studies support the idea that caloric compensation is less adequate for liquid calories compared to calories delivered in more solid form. Work from our laboratory using rats has examined the role that differences in diet viscosity may play in altering energy intake and body weight regulation. This work has suggested that when offered diets matched on caloric density, macronutrient and micronutrient composition, and differing only in viscosity, adult rats fail to compensate for calories delivered in low-viscosity form in short-term intake tests. Further, long-term consumption of low-viscosity diets leads to enhanced weight gain in adult rats. In the present studies, we examined whether short- or long-term exposure to varying relationships between viscosity and calories led to altered food intake or body weight regulation in juvenile rats. The results demonstrated that animals given either short- or long-term experience with direct relationships between viscosity and calories (high viscosity, high calorie meals and low viscosity, low calorie meals) did not differ in food intake or body weight gain compared to animals given short- or long-term experience with indirect relationships between viscosity and calories (high viscosity, low calorie meals and low viscosity, high calorie meals). When juvenile rats were given long-term (9 weeks) exposure to a single, high or low viscosity diet supplement, matched on caloric density and differing only in viscosity, there were no effects on body weight gain. However, analysis of body composition using DEXA demonstrated that animals consuming the low viscosity supplements had significantly greater body fat than animals that consumed either the high viscosity supplement or no dietary supplement at all. These differences in body fat persisted for at least 3 months following the cessation of dietary supplements; during this 3-month period, animals previously exposed to the low viscosity supplement also gained significantly more weight than animals previously exposed to the high viscosity supplement. Taken together, the results suggest that consuming calories in low viscosity form may contribute to poor intake regulation over the short-term and to increased adiposity over the long term. When animals experience these diets as juveniles, these effects may persist into adulthood.     

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

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

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.     

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.