Differential effects of medium- and long-chain triglycerides on food intake of normal and diabetic rats

Three experiments were performed to examine the effect of ingestion of medium- (MCT) and long-chain (LCT) triglyceride oils at the beginning of the normal feeding period on subsequent food intake of normal and diabetic rats. In the first experiment, diabetic rats reduced food intake more than normal animals in the first 6 hr after ingestion of 2.0 ml of MCT or LCT oil. In the second experiment, diabetic rats reduced food intake to a similar extent by 6 hr after ingestion of 1.5 ml of MCT or LCT oil, but the time course of this effect depended on the oil ingested. Ingestion of MCT oil produced a decrease in food intake within 2 hr, whereas ingestion of LCT oil reduced food intake 2–4 hr later. In the third experiment, a direct comparison was made of the differential time course of food intake suppression by MCT or LCT oil in both normal and diabetic rats. Diabetic rats decreased food intake after ingestion of 1.5 ml MCT or LCT oil, whereas normal rats did not. Again, in diabetic rats, ingestion of MCT oil produced a more rapid reduction in food intake than ingestion of LCT oil. It is proposed that the more pronounced reduction in food intake of diabetic rats after oil ingestion is due to a greater degree of hepatic oxidation of ingested fat, whereas the differential effect of MCT and LCT oil ingestion in diabetic rats is due to a differential rate of delivery of the ingested lipid substrate to the liver.     

Insulin counteracts the satiating effect of a fat meal in rats

The effects of insulin administration of the reduction on food intake which follows a meal of corn oil was examined in normal and streptozotocin-diabetic rats. In the first experiment, a single injection of long-acting, protamine zinc insulin (3 IU) curtailed the decrease in 24-hr food intake that occurred in normal and diabetic rats after ingestion of 2.0 ml of oil. In a second experiment, injection of short-acting, regular insulin (0.5 IU) prevented the depression of food intake which occurred 6-24 hr after ingestion of 1.5 ml of corn oil, but not at earlier time intervals. In a third experiment, the short-term suppression of food intake in diabetic rats that occurred within 6 hr after a 1.5 ml meal of oil was reduced by chronic administration of insulin (3 IU/day) via a subcutaneously implanted osmotic pump. The results indicate that a relatively long-lasting effect of insulin counteracts the satiation from ingested fat and suggest that insulin's role in the control of food intake may depend on the composition of the diet.     

Intragastric injections of partially digested triglyceride suppress feeding in the rat

The 30 min intake of a 50% corn oil emulsion was measured in 12 hr fasted Sprague-Dawley rats equipped with gastric tubes. When the subjects were given 5 ml intragastric injections of normal saline or of the same oil emulsion they drank by mouth their voluntary intake was unaffected. However, when they were injected with oil emulsion that had been previously ingested by donor subjects, they decreased their feeding significantly. These results suggest that the putative satiety receptors are not stimulated by undigested corn oil triglycerides but by a product of their digestion. This factor appears to be present in the oily rather than the aqueous fraction of the digested oil because when these fractions were given separately only the oily fraction induced inhibition of feeding. Finally, intragastric injections of predigested oil failed to act as an unconditioned stimulus in the development of taste aversions to neutral flavors. This suggests that the reductions in eating observed were not the product of malaise or discomfort.     

Food intake after intragastric meals of short-, medium-, or long-chain triglyceride

Food-deprived Sprague-Dawley rats were given equicaloric intragastric infusions of mixed meals consisting largely of short- (SCT), medium- (MCT), or long-chain triglyceride (LCT). When animals were allowed to feed 20 min after infusion, there was an immediate reduction of food intake that was sustained over the 2 hr feeding period. During the first hour of feeding, the SCT, which is digested and absorbed more rapidly than the MCT or the LCT, was more effective per calorie in reducing food intake than these longer-chain triglycerides. However, during the second hour, cumulative intakes after the different triglyceride infusions were not significantly different. Equicaloric infusions of the MCT and the LCT resulted in equivalent reductions of food intake at all times. The satiety effects of these two triglycerides appear to be related to their caloric properties rather than to chain length. Since the LCT reduced food intake before the absorbed fat could have entered the blood to stimulate satiety·signals, this satiety effect may be mediated by a gastroenteric signal. None of the triglyceride infusions resulted in a conditioned taste aversion suggesting that food intake was reduced through normal satiety rather than through discomfort.     

Behavioral and physiological consequences of intragastric oil feeding in rats

Four experiments were conducted to examine the appropriateness of intragastric feeding of vegetable oil. The first three experiments demonstrated that pairing intragastric feeding with a taste of saccharin, reduced subsequent saccharin preference slightly. A dose of lithium chloride which did not reduce food intake, produced a very strong conditioned aversion. It is therefore difficult to argue on the basis of taste aversions, that any reduction in food intake resulting from intragastric fat feeding is due to malaise. Intragastric fat feeding did not always reduce subsequent food intake; a large reduction in food intake was observed only when non-starved animals were given at least two previous spaced exposures to fat. The effects of oral and intragastric oil feeding on blood levels of triglycerides and free glycerol were examined. Blood triglycerides and glycerol rose sooner and fell sooner following intragastric than after oral oil feeding. Emulsifying the oil did not correct the abnormality; indeed it exaggerated the early rise in blood triglycerides and glycerol. These results indicate that interpretation of studies involving intragastric fat feeding is more complicated than generally recognized.     

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.     

Diabetes and a high-fat/low-carbohydrate diet enhance the acceptability of oil emulsions to rats

Acceptability of corn oil and coconut oil emulsions was examined in streptozotocin-diabetic (55 mg/kg, IP) and normal rats fed either a high-fat/low-carbohydrate (HF/LC) or low-fat/high-carbohydrate (LF/HC) diet. Intake of five concentrations of the emulsions (2.5, 5, 10, 20 and 40%) was measured in 30-min, one bottle intake tests. Diabetic rats consumed more of the oil emulsions than did normal rats. Emulsion intake by diabetic rats increased, then decreased across concentrations, whereas emulsion intake by normal rats showed little change across concentrations. No differences in the intake of corn and coconut oil emulsions were observed. Total oil consumption was higher in diabetic than in normal rats at the three highest emulsion concentrations. Total oil consumption was also higher in rats fed the HF/LC diet as compared to those fed the LF/HC diet. These findings suggest that the presence of diabetes or feeding a HF/LC diet can enhance oil emulsion intake of rats in short-term tests.     

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.     

Effects of insulin on food intake and plasma glucose level in fat-fed diabetic rats

Schedules of insulin treatment which reliably increased eating in fat-fed diabetic rats were studied for their effect on plasma glucose concentrations. An inverse correlation between intake and plasma glucose was observed in fat-fed diabetics given long-term treatment with protamine-zinc insulin (PZI); however changes in glucose did not account for the differential effect of insulin on food intakes in normal controls or normal and diabetic rats fed a low-fat food. A single injection of 1 U PZI which increased eating in fat-fed diabetics but not normal controls 17–23 hr later did not reduce glucose concentrations from hyperglycemic levels in diabetics during the same time period. Injections of regular insulin increased eating in fat-fed diabetic and normal rats in a comparable fashion, but did not reduce plasma glucose in diabetics as low as in normal animals. The results show that the effect of exogenously administered insulin on food intake in fat-fed diabetics is largely unrelated to changes in circulating glucose levels and suggest that metabolic consequences of insulin treatment other than hypoglycemia may underlie the effect of the hormone on feeding in these animals.     

Corn oil and mineral oil stimulate sham feeding in rats

To determine the orosensory effects of oils on ingestion, we measured the 1-bottle intake of corn oil and of mineral oil during 30 minutes of sham feeding in rats that were food deprived overnight or nondeprived. Rats sham fed both oils. Food-deprived rats ingested significantly more of both oils than nondeprived rats. Rats discriminated corn oil from mineral oil and as little as 0.78% corn oil emulsion from water. When rats sham fed 8 dilutions of corn oil, intake was an inverted-U function of concentration with maximal intakes produced by 12.5%, 25% and 50% corn oil emulsions. Despite similar, sometimes equal, intakes of corn oil and mineral oil in 1-bottle tests, food-deprived and nondeprived rats showed a strong preference for corn oil in 2-bottle, sham-feeding, preference tests. The sensory mechanisms that mediate the oral effects of oil on intake and preference are not known, but the olfactory and trigeminal sensory systems are the most likely candidates. Further work is required to characterize the potency, sensitivity, and discriminability of the orosensory effects of oils, the mechanisms that mediate them, and their role in the control of fat intake.     

Hypophagia following dietary obesity

Two experiments examined the hypophagia that occurs when rats are switched from a high-fat to a low-fat diet. In the first experiment, rats fed a high-fat diet for eight weeks weighed 79 g more than rats fed a low-fat diet. Removal of the high-fat diet led to reduced food intake for at least four weeks. Reducing the body weight of the rats by a 24 hour fast did not alter the time course of the hypophagia. Plasma levels of free glycerol, free fatty acids and ketones were elevated during and after feeding the high-fat diet; suggesting that feeding a high-fat diet increases fat oxidation even after the high-fat diet is withdrawn. In the second experiment, feeding rats the high-fat diet for four weeks increased body weight and body fat. Starving the rats for two days after feeding the high-fat diet did not alter subsequent hypophagia and did not alter the percentage of body fat. This pattern of results is similar to that previously seen following termination of obesity-inducing insulin treatment. The results are consistent with the idea that a persistent increase in fat oxidation is responsible for the hypophagia.     

Effects of estradiol on food intake and meal patterns for diets that differ in flavor and fat content

Apart from the well known inhibitory effects of estradiol on food intake, meal size, and body weight in female rats that have been documented over the past thirty years, a more recent report presents the opposite finding; that a large dose of estradiol can increase food intake and weight gain in gonadally intact female rats presented with a palatable diet. The purpose of the present experiment was to further examine this hypothesis by evaluating the ability of estradiol to influence feeding behavior in ovariectomized rats presented with diets that differ in flavor and fat content. Female rats were given a cyclic regimen of estradiol benzoate treatment (5.0 or 20.0 µg) or the oil vehicle and were presented with the standard chow diet or a diet with a higher fat content and chocolate flavor. Food intake, meal size, and meal number were monitored three days after the first injection of estradiol or oil. Compared to the chow diet, food intake increased when animals had access to the chocolate/fat diet during the vehicle treatment condition. Both doses of estradiol significantly decreased food intake, meal size, and body weight gain when animals were presented with either the standard chow diet or the chocolate/fat diet. These findings indicate that estradiol does not stimulate the intake of a palatable diet in ovariectomized rats, and suggest that previous results showing that estradiol enhanced eating and weight gain stemmed from a disruption of the hypothalamic-pituitary-gonadal axis when intact females received a large dose of exogenous estradiol.     

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.     

D-galactosamine hepatotoxocity. V. Role of free fatty acids in the pathogenesis of fatty liver

The role of free fatty acids (FFA) in the pathogenesis of fatty liver was investigated in female rats who received a single ip injection of d-galactosamine-HCl, (GalN), 750 mg/kg body weight. Groups of rats were either fasted for 14 hr prior to GalN injection and then fasted for the duration of the experiment or were fed ad libitum prior to and after GalN administration. Plasma FFA were determined in groups of fasting or fed rats sacrificed at intervals between 0 and 24 hr after GalN administration. The results revealed a progressive increase in plasma FFA in GalN-injected fasted rats (0 hr, 0.40 μmol/ml; 24 hr, 1.09 μmol/ml) whereas in fed animals only a modest increase in plasma FFA concentrations occurred. Hepatic triglyceride content was determined in groups of fasted and fed rats at 6 and 24 hr after GalN administration. Hepatic triglycerides, in fasted rats, were increased 7-fold at 6 hr (22.4 ± 8.5 mg/g) and were markedly increased at 24 hr (114.8 ± 18.4 mg/g). In contrast, feeding protected the rats from the development of fatty liver since hepatic triglycerides were only twice controls at 6 hr and 4-fold increased 24 hr after GalN. Ultrastructural studies were performed at 15, 24, and 48 hr after GalN in fed and fasted rats. Electron microscopy disclosed hepatocellular necrosis and profound fat accumulation in the fasted animals; however, feeding afforded marked protection against the development of fatty liver and hepatic injury. The results of these studies indicate that the GalN-induced fatty liver is associated with a sustained elevation of plasma FFA. The increase in plasma FFA can be prevented by feeding the animals prior to and after GalN administration suggesting that a stimulus for FFA elevation may be the alterations in carbohydrate metabolism known to be induced by GalN in rat liver.     

Gustation as a factor in the ingestion of sweet and fat emulsions by the rat

This paper was written to pay honor to Professor Gerard P. Smith because of his strong influence on me to study the ingestion of sweet and fat mixtures. Three experiments are reported here, in which the laboratory rat was given an emulsion of a glucose+saccharin mixture with corn oil. In the first experiment, a two-bottle, 24-h test was given comparing the emulsion with water. Over 6 weeks, the concentration of the corn oil was gradually increased. When given only food and water, or the glucose/saccharin solution, the rats regulated their caloric intake and grew at a normal rate. In contrast, when the corn oil was present, the rats significantly increased their caloric intake, resulting in a marked increase in body weight. In the second experiment, a detailed analysis of the ingestion revealed that the rate of licking the emulsion during drinking bouts increased in a linear manner as the concentration of the corn oil was increased. In the third experiment, a conditioned taste aversion to the sweet/fat emulsion generalized to the fat more than to the sweet solutions. The implications for a gustatory input are discussed.     

The satiety effects of intragastric macronutrient infusions in fatty and lean Zucker rats

To evaluate satiety in the hyperphagic, genetically obese Zucker “fatty” (fafa) rat, food-deprived fatty and lean (FaFa) control rats were given equicaloric intragastric infusions consisting largely of fat, carbohydrate, or protein. Relative to distilled water infusion, these infusions resulted in immediate reductions of food intake in both fatty and lean rats allowed to feed 20 min post-infusion. Cumulative food intakes remained reduced throughout the 2 hr period of observation. Thus, despite its hyperphagia, the fatty rat is responsive to the satiating effect of infused nutrients. However, the relative satiating effectiveness of the macronutrient infusions differed for the two genotypes. In lean rats, the different macronutrient infusions resulted in equivalent reductions of feeding. In contrast, in fatty rats, fat was the least satiating and protein was the most satiating macronutrient. Moreover, compared to lean rats, fatty rats displayed less initial suppression of feeding after fat infusion and greater overall suppression after protein infusion. These effects are consistent with the long-term feeding behavior of the fatty rat for the different macronutrients and may be related to pre- and postabsorptive metabolic alterations that have been documented in this animal.     

Effects of comfort food on food intake, anxiety-like behavior and the stress response in rats

It has been suggested that access to high caloric food attenuates stress response. The present paper investigates whether access to commercial chow enriched with glucose and fat, here referred to as comfort food alters behavioral, metabolic, and hormonal parameters of rats submitted to three daily sessions of foot-shock stress. Food intake, anxiety-like behaviors, and serum levels of insulin, leptin, corticosterone, glucose and triglycerides were determined. The rats submitted to stress decreased the intake of commercial chow, but kept unaltered the intake of comfort food. During the elevated plus maze (EPM) test, stressed rats increased the number of head dipping, entries into the open arms, as well as the time spent there, and decreased the number of stretched-attend posture and risk assessment. These effects of stress were independent of the type of food consumed. Non-stressed rats ingesting comfort food decreased risk assessment as well. Stress and comfort food increased time spent in the center of the open field and delayed the first crossing to a new quadrant. Stress increased the plasma level of glucose and insulin, and reduced triglycerides, although consumption of comfort food increases glucose, triglyceride and leptin levels; no effect on leptin level was associated to stress. The stress induced increase in serum corticosterone was attenuated when rats had access to comfort food. It was concluded that foot-shock stress has an anorexigenic effect that is independent of leptin and prevented upon access to comfort food. Foot-shock stress also has an anxiolytic effect that is potentiated by the ingestion of comfort food and that is evidenced by both EPM and open field tests.     

Vigorous intake of oil emulsion caused by chronic food deprivation remains after recovery in rats

Oil emulsion intake over a 30-min period was compared under different dietary conditions (ad libitum feeding and chronic food deprivation) and at various concentrations of oil in rats. The pattern of intake for each dietary condition was extremely different. Food-deprived rats ingested more emulsion when the solution was thicker but intake amount became less at too high a concentration. Ad libitum feeding rats ingested less emulsion than deprived rats with no difference among the concentrations. Rats on a restricted diet clearly differentiated between concentrations, selecting the thicker emulsion when provided two-bottle selection between 10% oil and some other concentration. On the other hand, rats fed ad libitum differentiated between only extremely weak solutions. The vigorous intake of oil emulsion induced by chronic food deprivation was maintained after 2 weeks of normal feeding. Significant difference between prior dietary conditions was maintained at lower concentrations. Dietary timing for food-deprived rats affected little on emulsion intake. These results indicate that response to oil emulsion intake differs by concentration in rats.     

Transient overconsumption of novel foods by deafferentated rats: effects of novel diet composition

We recently demonstrated that capsaicin-treated rats consume more of an unfamiliar high-fat diet than vehicle-treated controls, but only on initial exposure (Chavez et al, 1997). We hypothesized that negative feedback signals carried by capsaicin-sensitive visceral afferents are critical for the regulation of intake of novel foods, but redundant pathways take over during subsequent exposures. To examine the role of nutrient content of the novel diet, rats were systemically treated with capsaicin (n = 15) or vehicle (n = 10), and exposed to 1) a fat/olestra diet that was isocaloric with chow; 2) a readily accepted fat-free cake; and 3) pure corn oil. Each 3-h feeding trial was preceded by 24-h food deprivation. Treated rats did not overconsume familiar chow, but did consume 50% more than controls of both the fat/olestra diet and the corn oil on first exposure; this suggests that capsaicin eliminated visceral afferents that normally carry satiety signals. However, the effect with the fat/olestra mixture was due primarily to depressed intake by controls, unlike the pure fat diets; this apparent neophobic response was blunted in treated rats. Because treated rats failed to overconsume the fat-free cakes, the neural system damaged by capsaicin appears to be linked to energy or fat sensory mechanisms, and possibly to hedonic responsiveness.     

Suppression of food intake by intragastric glucose in rats with impaired glucose tolerance

Three experiments were performed to examine the relationship between impaired glucose tolerance and food intake. In the first experiment, normal rats that were given long-term insulin treatment, which was then withdrawn, ate less than controls when refed after food deprivation. Despite reduced intakes, rats previously treated with insulin became more hyperglycemic than controls during refeeding. In the second experiment, intragastric glucose injections reduced food intakes to a similar degree in control rats and in rats experiencing insulin withdrawal even though glucose loading produced a much greater increase in plasma glucose level in previously insulin-treated rats. In the third experiment, intragastric loads of a glucose polymer, Polycose, reduced food intake to the same degree in normal rats and in streptozotocin-diabetic rats both two and sixteen days after insulin withdrawal when diabetic rats were, respectively, hypo- and hyperphagic. The results show that impaired glucose tolerance does not appreciably alter the suppressive effects of glucose loading on food intake. Other effects of glucose administration, besides those on insulin-dependent glucose utilization, appear to reduce food intake after glucose loading.