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.     

Lack of beneficial effects of wheat bran cereals on cholesterol balance in swine

Twenty young (8–10 weeks old and approximately 10 kg) male Yorkshire swine were studied for (1) the effects of the amounts of fat (90, 30, and 0 g butter) added in mash-based diet on serum cholesterol concentrations and fecal neutral steroids and bile acid excretions; (2) the effects of fat in semipurified diets with the same amount of dietary fiber as in mash but derived from wheat bran cereals in the semipurified diets; and (4) the effects of a wheat bran cereal containing a high lignin content. The effects of fat contents on serum cholesterol concentration and fecal steroid excretions were demonstrated in both mash-based diets and in semipurified diets containing wheat bran cereal as the source of dietary fibers. Butter (90 g) added to a mash-based diet resulted in an increase in serum cholesterol concentration and a reduction in fecal steroids as compared to the 0-g butter group. When fat content was varied in a semipurified diet containing wheat bran cereal, serum cholesterol concentrations were elevated during 40 and 20% fat (by calories) diet periods accompanied by the reduction in fecal steroid excretions. On comparing fecal steroid excretions in wheat bran-containing diets and in mash with dietary fiber content of both at 64 g and equal fat contents, wheat bran-containing diets excreted significantly less than mash. Moreover, fecal steroid excretions during wheat bran diets were essentially the same as that of a semipurified diet containing purified cellulose-type fiber as the source of fiber. However, at the low fat content (10% fat by calories), bran-containing diet produced fecal bulk similar to that of mash. A wheat bran cereal containing higher (2.6 times) lignin content than the other did not affect fecal steroid excretion. It appears, therefore, that higher fecal steroid excretion during mash feeding is not principally due to fiber per se but due to factor(s) yet to be named. From our studies on the effects of soy protein, vegetable proteins in mash might be the factor mainly responsible for increased fecal steroid excretions.     

Dietary fat and obesity: a review of animal, clinical and epidemiological studies

The First Law of Thermodynamics provides a framework for understanding the imbalance between energy intake and expenditure that produces obesity, but it does not help understand the role of genetics, the regulation of food intake, the distribution of body fat, the mechanisms by which diets work or the mechanism by which portion control has gotten out of control. In animals, increasing dietary fat increases body fat, and it is unlikely that humans escape this important biological rule. In epidemiological studies, increasing dietary fat is associated with increased prevalence of obesity probably by increasing the intake of energy dense foods. In the National Weight Loss Registry, three things were associated with weight loss: continued monitoring of food intake, lowering dietary fat intake, and increased exercise. The relation of dietary fat is most evident when physical activity is low. The speed of adaptation to dietary fat is increased by exercise. When dietary fat is reduced, weight is lost, but weight loss eventually plateaus. The rate of weight loss during the initial phase is about 1.6 g/day for each 1% decrease in fat intake. When dietary fat is replaced with olestra to reduce fat intake from 33% to 25% in obese men, weight loss continues for about 9 months reaching a maximum of nearly 6% of body weight and a loss of 18% of initial body fat. In the control group with a 25% reduced-fat diet, weight loss stopped after 3 months and was regained over the next 6 months, indicating the difficulty of adhering to a conventional low-fat diet. Thus, dietary fat is an important contributor to obesity in some people.     

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.     

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.     

Variation of fat intake with estrous cycle, ovariectomy and estradiol replacement in hamsters (Mesocricetus auratus) eating a fractionated diet

Intakes of fats, proteins, and carbohydrates were measured daily for a 3 month period in female hamsters maintained on a fractionated diet consisting of the dietary constituents, dextrose, fat and soybean meal. In the first study, hamsters showed variations in body weight and fat intake across the estrous cycle and following ovariectomy, with elevations during diestrous and after ovariectomy when endogenous estrogens are reduced. In the second study, the effects of exogenous estradiol or cholesterol on intake patterns of ovariectomized hamsters were determined. Hamsters lost weight and decreased fat intake when implanted with a silastic containing estradiol and gained weight and increased fat intake when exposed to cholesterol treatment. In neither of the two studies were the intakes of protein or carbohydrates significantly affected by the animals' hormonal status. These results suggest that in the hamster, estrogenic effects on food intake are specific to some dietary constituents and not to others.     

Appetite suppression through delayed fat digestion

High-fat diets are often associated with greater caloric intake and weight gain. Since satiety during fat intake is induced by fat in the intestine we investigated the efficiency of a lipid compound that retards fat digestion to regulate fat intake. We found this compound to reduce high-fat food intake, body weight and blood lipids in Sprague-Dawley rats, without causing steatorrhea. The absence of steatorrhea is explained by an increased pancreatic lipase/colipase secretion, compensating the impaired lipolysis by the added compound. The animals also had an elevated CCK secretion. The satiety for fat may be the consequence of elevated CCK and procolipase/enterostatin levels. We conclude that compounds can be found that delay intestinal fat digestion and control high-fat food intake through the release of satiety signals, without causing steatorrhea. The absence of steatorrhea makes such compounds advantageous over lipase inhibitors in the treatment of obesity.     

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.     

Apolipoprotein A-IV, food intake, and obesity

Apolipoprotein A-IV (apo A-IV) is secreted by the intestine associated with chylomicron. Intestinal apo A-IV synthesis is stimulated by fat absorption, which is probably mediated by chylomicron formation. The stimulation of apo A-IV synthesis in the jejunum and ileum is attenuated by intravenous leptin infusion. Intestinal apo A-IV synthesis is also stimulated by a factor from the ileum, probably peptide tyrosine-tyrosine (PYY), which has been demonstrated to affect satiety. Apo A-IV has been proposed to physiologically control food intake, a function not shared by apo A-I, and this inhibitory effect is centrally mediated. Recently, apo A-IV was demonstrated in the hypothalamus. The hypothalamic apo A-IV level was reduced by food deprivation and restored by lipid feeding. Intracerebroventricular administration of apo A-IV antiserum increased feeding and decreased the hypothalamic apo A-IV mRNA level, implying that feeding is normally limited by endogenous apo A-IV. Central administration of neuropeptide Y (NPY) significantly increased hypothalamic apo A-IV mRNA levels in a dose-dependent manner. The stimulation of intestinal synthesis and secretion of apo A-IV by lipid absorption are rapid; thus, apo A-IV is capable of short-term regulation of food intake. Evidence also suggests apo A-IV's involvement in the long-term regulation of food intake and body weight. Chronic ingestion of high fat blunts the hypothalamic apo A-IV response to lipid feeding and may therefore explain why chronic intake of high fat predisposes animals and humans to obesity.     

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 behavior in rats fed diets containing medium chain triglyceride.

The effect of dietary medium chain triglyceride (MCT) on short-term food intake was compared with the effect of long chain triglyceride (LCT) in rats. Corn oil and glyceryl tricaprylate were used as LCT and MCT sources, respectively. Rats were given diets containing 200 g MCT/kg diet (MCT diet), 100 g MCT + 100 g LCT/kg diet (ML diet), or 200 g LCT/kg diet (LCT diet) in Experiment 1. Cumulative food intake was determined every h for the first 12 h, then at 2-h intervals thereafter during the subsequent 12 h. As early as 1 h after feeding, cumulative food intake significantly decreased in MCT-fed animals in a dose-dependent fashion. In Experiment 2, rats were given a choice between MCT and LCT diets for 1 h to confirm whether or not the palatability of diets was influenced by dietary fat sources. There was no difference in food intake between the two diets. In Experiment 3, the responsibility of endogenous cholecystokinin (CCK) for the difference in food intake between the two diets was investigated for 6 h by using a CCK-A receptor antagonist, Devazepide (DVZ, 1 mg/kg b. wt.). Food intake in the MCT diet and also in the LCT diet was improved by DVZ. It is concluded that the satiety, but not the palatability, is affected by carbon chain length in dietary triglyceride sources, although the responsibility of endogenous CCK is very small.     

Trafficking of dietary fat and resistance to obesity

The task of maintaining energy balance involves not only making sure that the number of calories ingested equals the number of calories burned but also involves ensuring nutrient balance. This means that over time, the quantity of carbohydrate, fat and protein consumed equals the amount of each oxidized. While the body has the ability to convert protein to carbohydrate and carbohydrate to fat, over long periods of time the body establishes nutrient balance with a high degree of accuracy storing excess nutrients as fat. To make decisions about food intake, the brain must assimilate information about the quantity of nutrients ingested and their disposition through the body over time. This is a very complex time ordered process as different tissues may be in different states of energy balance at different intervals following food ingestion. The fundamental task for the brain is to assess the influx of nutrients relative to stored pools of those nutrients and the rate at which they are being oxidized. It has been suggested that this task is particularly difficult for dietary fat because the stored pool of lipid is quite large compared to either the stored pools of carbohydrate and protein or the quantity of fat ingested per day. It is clear that some organisms resist weight gain even in the face of highly palatable diets. In fact most individuals eat less on any given day than they could given their maximal capacity for consumption. A central question then is: what restrains food intake in the setting of widely available highly palatable food? In this paper we will discuss the evidence that the movement of dietary fat between tissues may play an important role in the fidelity of nutrient sensing and as a result, resistance or susceptibility to obesity. In particular, the relative metabolism of dietary fat favoring oxidation over storage may be associated with more robust signaling of positive energy balance and resistance to dietary induced obesity in both humans and rats.     

Nutritional requirements of infants and children with respect to cholesterol and related compounds

Cholesterol is an enigmatic, essential metabolite. Breast milk contains significant quantities of cholesterol, yet human infants thrive on cholesterol-free diets. Recommendations to lower serum cholesterol are widespread, yet low serum cholesterol is associated with poorly understood morbidity. Serum cholesterol is increased with diets high in fat, yet dietary cholesterol has relatively little effect on serum concentrations. Smith-Lemli-Opitz syndrome, marked with extremely low serum cholesterol, may serve as a human model for the evaluation of absorption and metabolism of dietary cholesterol. © 1994 Wiley-Liss, Inc.     

Age, sex and reproductive status alter the severity of anorexia in zinc deficient rats

Food intake and body weight gain in rats fed a zinc-deficient diet are reported. The severity of zinc deficiency-induced anorexia was observed to be dependent upon the age, sex and reproductive status of the animal. Rapidly growing rats such as weanlings, adult males, or ovariectomized females demonstrated more rapid induction of anorexia and more severe effects on cumulative food intake and body weight gain when fed zinc-deficient diets than did slowly growing (nonpregnant female adult) rats given the same diet. These results suggest that feeding in zinc-deficient animals is not regulated by dietary zinc concentration alone, but rather is mediated by one or several as yet undefined factors.     

Food intake,body composition and blood lipids following treadmill exercise in male and female rats

Body weight gain, food intake, body composition and blood lipids of male and female Osborne Mendel rats were compared on the same exercise treadmill program. To mimic their nocturnal habits, rats were exercised daily at the beginning of the 12 hour dark cycle and food intake was measured for both light and dark cycles. After a 10 day treadmill adaptation period, the duration of exercise was successively increased over a 12 day period until 60 min/day at 21.3 meters/min was reached. Relative to their respective controls, exercised male rats showed a reduction in body weight and light cycle food intake while female runners showed no change in body weight or food intake. Exercise resulted in a decrease in percent body fat in both males and females while only male runners increased percent protein. Both males and females reduced serum triglycerides while serum cholesterol was reduced only in the males. The short term exercise program produced highly significant changes in the males while the females were more resistant to the same exercise regimen.     

Two weeks of dietary supplementation with green tea powder does not affect performance, d-xylose absorption, and selected serum parameters in broiler chickens

The aim of the present study was to investigate the putative effects of dietary supplementation with green tea powder on growth performance, d-xylose absorption as well as serum-selected parameters of broiler chickens. Forty 21-day-old chickens were randomly allocated into four groups and fed with diets supplemented with 0% (control), 1%, 2%, or 4% green tea powder for 2?weeks. At the end of the experiment, d-xylose absorption test was performed on all birds on a 45-min basis for 135?min, and PCV as well as serum total protein, total cholesterol, LDL-c, HDL-c, triglycerides, iron, calcium, and phosphorus concentrations were assayed. Body weight, feed intake, and feed conversion ratio (FCR) were also recorded during the experiment. No significant differences were observed in plasma d-xylose concentrations, PCV, or serum parameters among different groups (p?>?0.05). Differences in body weight, feed intake, and FCR were insignificant as well. In conclusion, dietary supplementation with green tea powder for 2?weeks has no adverse effect on PCV, intestinal absorption of d-xylose, serum total protein, lipid profile, and mineral concentrations as well as performance parameters of broiler chickens.     

Aversion of the cat to dietary medium-chain triglycerides and caprylic acid

Young, specific-pathogen-free cats were fed purified diets containing different sources of fat. Food intake was depressed and cats lost weight when the diet contained either hydrogenated coconut oil (HCO) or medium-chain triglycerides (MCT). With an MCT preparation enriched in 8:0 (MCT8), cats would not eat after first tasting the diet. When cats were offered a choice of two high-fat diets, they chose the basal diet over a diet containing 30% HCO, by a ratio of 4.5:1. Low levels of MCT8 (5% or 10% by weight) were also rejected, whereas cats did not reject 5% or 15% MCT12. Caprylic acid, at 0.1-1.0% of the diet, was rejected. In other studies, food intake and body weight decreased when HCO was added to a fat-free diet. Cats fed 25% or 35% HCO lost weight. When 5% safflower seed oil was added to the HCO diets, body weights and food intake improved, but were still less than optimal. These studies indicate that the food intake depression in cats fed dietary HCO and MCT is primarily a result of impalatability, and that the fatty acid moiety may be responsible for the aversion.     

Galanin type 1 receptor knockout mice show altered responses to high-fat diet and glucose challenge

Galanin, a brain and pancreatic peptide with three receptor subtypes (GALR1, GALR2, and GALR3), is hypothesized to participate in energy homeostasis and glucoregulation. Hypothalamic galanin expression is induced by dietary fat, and intra-hypothalamic galanin administration has orexigenic/anabolic properties. Systemic galanin infusion alters glucoregulation in non-human species, partly through direct actions on pancreatic islets. However, the physiologic significance of endogenous galanin-GALR signaling is unclear. The present studies tested the hypotheses that GALR1 deficiency alters food intake and feed efficiency following switches to high-fat diet and that GALR1 deficiency alters whole-body glucose homeostasis. Adult, male GALR1 knockout (-/-), heterozygote (+/-), and C57BL/6J control (+/+) mice were studied. GALR1 deficiency impaired adaptation to a 3-day high-fat diet challenge, leading to increased food intake, feed efficiency and weight gain. However, during the following 2 weeks, GALR1 knockout mice decreased intake, consuming less daily energy than while maintained on low-fat diet and also than heterozygote littermates. Chow-maintained GALR1 knockout mice showed relative hyperglycemia in fed and d-glucose (i.p. 1.5 g/kg)-challenged states. GALR1 knockout mice showed normal food intake, feed efficiency and weight accrual on low-fat diets, normal fasted glucose levels, and normal glucose sensitivity to porcine insulin (i.p. 1 IU/kg) in vivo. The results support the hypotheses that galanin-GALR1 systems help adapt food intake and metabolism to changes in dietary fat and modulate glucose disposition in mice.     

Effect of hydroxycitrate on food intake and body weight regain after a period of restrictive feeding in male rats

We examined whether dietary supplementation of hydroxycitrate (HCA), a competitive inhibitor of the extramitochondrial enzyme ATP-citrate-lyase, which inhibits lipogenesis, reduces food intake and body weight regain in rats after 10-15% weight loss. In four experiments, 24 male rats were fed restrictively (10 g/day) for 10 days and then given ad lib access to one of four different diets (HI-Suc=high sucrose; HI-Glu=high glucose; Chow=grounded standard rat chow; HI-Glu+Fat=high glucose+fat) varying in the content of fat and low molecular carbohydrates for the following 10 days. For half of the rats (n=12), the ad lib diet was supplemented with 3% (w/w) HCA. HCA reduced body weight regain with all diets except Chow. HCA also reduced food intake temporarily with three of the four tested diets. The suppressive effect of HCA on food intake was particularly strong with the HI-Glu+Fat diet (fat=24% of energy). With Diet HI-Glu and HI-Glu+Fat HCA reduced the feed conversion efficiency (cumulative body weight regain (g)/cumulative food intake (MJ)) during the 10 ad lib days, suggesting that it also increased energy expenditure. This effect seemed to be positively related to the glucose content of the diet. All in all, HCA reduced body weight regain after substantial body weight loss, and the effects are presumably linked to its inhibiting effect on lipogenesis, but the exact mechanism still has to be determined.     

Suppression of weight gain by glucagon in obese Zucker rats

Glucagon has been shown to lower blood lipids and to decrease food intake and body weight in short-term studies in man and animals. There is evidence of decreased secretion of glucagon in human obesity. The Zucker obese rat suffers from a genetic type of obesity and has an absolute reduction in circulating glucagon concentration. The effect of long-term administration of glucagon on the body weight in obese Zucker rats was studied. Glucagon caused a marked (-20%) reduction of body weight in obese Zucker rats with no change in feed intake. Urine glucose, urea nitrogen, creatinine, and ketone content, as well as serum triglyceride, cholesterol, alkaline phosphatase, creatinine, and insulin levels remained unchanged. Weights of perirenal fat, kidneys, and heart also remained unchanged. However, glucagon injection in obese Zucker rats caused significant decrease in serum glucose, and increases in SGOT, liver weight, and liver lipid and glycogen content. Further investigations are needed concerning the safety of chronic glucagon administration for weight control.