Effect of chronic insulin administration on food intake and body weight in rats.

Insulin was chronically administered to rats to determine its effect on the daily changes in food intake and body weight. Animals received regular insulin via 14-day osmotic minipumps in doses of 0.0, 0.5, 1.0, 3.0, and 5.0 IU/day treated either with (+GLU) or without glutamic acid (-GLU). Previous studies have shown that glutamic acid prevents insulin aggregation in the minipumps to provide a more stable flow rate. Food intake and body weights were measured each day of treatment. Chronic insulin treatment was ineffective in promoting changes in animals receiving any dose of insulin except the highest dose. Animals receiving 5.0 IU/day insulin + GLU experienced a transient hyperphagia and weight gain followed by a suppression in food intake and body weight by Day 4 of treatment. Effects were attenuated in animals receiving insulin -GLU. Plasma insulin concentrations on Day 14 were similar for all doses, suggesting a compensation took place either in insulin degradation or endogenous insulin production. Results indicate that glutamic acid treatment enhances the effects of chronic insulin administration via osmotic minipumps.     

Copulation affects body weight but not food intake or dietary self-selection in male rats

The mechanisms responsible for copulation-induced changes in body weight were investigated using adult male rats. Animals that copulated two or three times a week for 6 weeks gained less weight than sexually inactive controls. The reductions in body weight gain were not associated with changes in total caloric intake or the intake of specific nutrients. Adipose tissue lipoprotein lipase activity was not affected by sexual activity. Based upon these results and previous observations, we suggest that copulation-induced reductions in body weight may not be mediated solely by testicular testosterone.     

Effects of dietary dehydroepiandrosterone on food intake and body weight in rats with medial hypothalamic knife cuts

Dehydroepiandrosterone (DHEA) is a steroid which has been reported to have anti-obesity effects when added to the diets of rats and mice. In this report, rats made hyperphagic with medial hypothalamic knife cuts were placed on a diet containing 0.45% DHEA or a control diet. Knife cut rats on the control diet ate more food and gained more weight than sham-operated rats on the control diet. In contrast, knife cut rats fed the DHEA diet weighed the same as shams on the DHEA diet and were only observed to be hyperphagic on one of eight 24 hour measurements taken during a five week period. Dietary DHEA reduced food intake and body weight of both knife cut and sham-operated rats, though the effects were smaller in shams. As these effects of DHEA were reminiscent of the effects of dietary quinine adulteration on intake by knife cut rats, a second experiment measured the food intake of unoperated rats when given a choice between a control high-fat diet and one adulterated with various concentrations of DHEA. Even at a concentration of 0.05%, rats clearly identified and avoided the DHEA-adulterated diet. While these results do not rule out effects of DHEA on metabolic rate or lipogenesis, they do indicate that the unpalatability of DHEA-adulterated diets may be a contributing factor in the observed effects on food intake and body weight.     

Wheel running, food intake, and body weight in male rats

The acquisition of wheel running, its effects on food intake and body weight, and the effects of wheel deprivation, were examined in male rats. Running increased during the first 15 days of access, then plateaued. When wheels were unlocked after 10 days of deprivation, running was reduced, but quickly recovered to original levels. Animals first given wheel access 49 days into the study ran little, with no increase over days. Food intake dropped each time with wheel access, but recovered to control levels over 10-14 days. Wheel deprivation resulted in a temporary hyperphagia. With wheel access, weight initially dropped and was then maintained at a reduced percentage of homecage-housed animals. In male rats wheel access appears to have temporary effects on food intake, and long term effects on weight. Marked differences in the activity of same-age rats suggest that wheel running is in part a function of housing history.     

The effects of estradiol on body weight and food intake in normal weight VMH-lesioned rats.

The effects of estradiol on food intake and body weight were examined in ovariectomized and VMH-lesioned, ovariectomized rats that were prevented from supranormal weight gain by food restriction. Estradiol injections that were effective in reducing weight in supranormal weight, ovariectomized rats had no effect on weight in normal weight, ovariectomized or VMH-lesioned, ovariectomized rats. Estradiol did not prevent hyperphagia and weight gain in VMH-lesioned, ovariectomized rats when they were provided with ad lib food.     

Signals that influence food intake and body weight

Energy homeostasis is a complex on-going process that includes maintaining immediately available as well as stored nutrient levels at optimal levels given the environment. To accomplish this, the brain receives continuous information about stored energy and current and anticipated fluxes in critical organs, as well as about food that is potentially available or being eaten and absorbed. The brain in turn determines when and how much food will be consumed, balancing this activity with other behaviors. This review discusses hormonal and related satiety signals generated as food is being consumed, and upon adiposity signals related to the amount of fat stored in the body, that influence energy intake and ultimately body weight.     

Effect of treadmill exercise on food intake and body weight in lean and obese rats

Body weight and food intake of lean and obese, male and female Osborne-Mendel rats following treadmill exercise were compared. Rats were assigned, separately by sex, to one of three diet groups; Group 1 was fed a low fat (10%) diet throughout the study, Group 2 was fed a high fat (55%) diet for 16 weeks and then switched to the low fat diet 1 week prior to exercise, and Group 3 was fed the high fat diet throughout the study. To control for differences in work output between the leanest and heaviest animals, exercise intensity was adjusted across groups such that all exercised rats had equivalent energy expenditure. After a 3 day training period, the exercise was successively increased over 8 days until a work output of 374.9J was reached. Relative to their respective controls, obese exercised males showed a reduction in body weight but no change in food intake. In contrast, exercised females showed no change in body weight or food intake, regardless of dietary condition.     

Peptidoglycan fragments decrease food intake and body weight gain in rats.

We hypothesized that peptidoglycan (PG) fragments decrease appetite in rats. Male Lewis rats (150 g; n > or = 7) received intraperitoneal (i.p.) injections of purified soluble PG fragments that had been treated with polymyxin B-agarose to remove residual endotoxin. Food consumption and body weight gain were determined at intervals after injection. Single i.p. injections of macromolecular extensively O-acetylated PG (S-O-PG) and non-O-acetylated PG fragments (24 to 240 micrograms/kg) reduced food intake and body weight gain in a dose-dependent fashion during the first 12 h after injection. Low-molecular-weight disaccharide peptide monomers with nonreducing 1,6-anhydro-N-acetylmuramic acid ends and muramyl dipeptide (MDP; 1.6 mg/kg) were also appetite and weight gain suppressants, albeit at least 10-fold less potent than S-O-PG; however, muramidase-derived monomers and peptide cross-linked dimers with reducing muramic acid ends were inactive. Appetite suppression was not limited to the Lewis rat strain since another strain, F344, exhibited similar decreases in food intake after injection of S-O-PG or MDP. Oral administration of MDP or S-O-PG, at concentrations 3 and 20 times higher, respectively, than those that were active i.p., failed to elicit a hypophagic response. We conclude that soluble PG fragments are potent suppressants of food consumption and body weight gain in rats and that, although macromolecular PG is more potent than low-molecular-weight fragments, neither O-acetylation nor glycosidic linkage of PG fragments is required for activity. We speculate that PG fragments may contribute to loss of appetite during bacterial illness.     

Effects of aldosterone and deoxycorticosterone on food intake and body weight

Aldosterone (.25 mg/kg) or deoxycorticosterone (3 mg/kg) in combination with corticosterone was administered daily to female adrenalectomized rats. The mineralocorticoids increased food intake and weight gain well beyond that of controls receiving only corticosterone injections. The weight gain was not wholly dependent on increased food intake, as separate groups of animals maintained on a restricted (10 g of laboratory chow/day) diet also displayed significant mineralocorticoid-stimulated weight gain. Although carcass composition was not directly determined, the undifferentiated wet/dry tissue ratios, hematocrit values, and nasoanal lengths found across groups suggest that the observed effect of mineralocorticoids was on body fat. Aldosterone and deoxycorticosterone can have important actions on energy metabolism as well as on sodium regulation.     

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.     

Effect of voluntary wheel exercise on food intake,water intake,and body weight for C57BL/6J mice and mutations which differ in maximal body weight

The relations of voluntary wheel exercise, food intake, water intake, metabolic rate, and body weight were determined for mutant mice (bg, c^J, A^y, and ob) with C57BL/6J genetic background and also for littermate controls. Mutant groups high in body weight (A^y and ob) had lower metabolic rates, were less active, and ate more food than controls. The nonobese mutants (c^J, and bg) had higher metabolic rates than controls, but different behavioral mechanisms for control of body weight during voluntary wheel exercise. Voluntary wheel activity for the albino (c^J) mice was similar to that of controls, but food intake increased proportionally more for albinos than controls. Food intake was similar for beige (bg) mutants compared with controls, but the beige group engaged in less voluntary wheel activity than controls.     

Cervical lymph nodes and mast cells in the marsupial Sminthopsis crassicaudata.

A study of the cervical lymph nodes from the fat-tailed dunnart, Smithopsis crassicaudata, revealed the nodes were pigmented with lipofuscin and contained many large cells which were identified as mast cells from their ultrastructure and histochemical staining properties. It is believed that the very high density of mast cells in the cervical lymph nodes contributed to an increase in size of these organs compared to other animals. Very high levels of histamine (90 micrograms/g) were found in the nodes. Cervical lymph nodes with these unusual features were found not only in healthy, umprimed laboratory bred adults, but also in pouch young, wild caught animals, and adults of the closely related species, Sminthopsis macroura. A comparison of the histochemical and ultrastructural characteristics of mast cells from various organs of adult S. crassicaudata was also made. Mast cells from lymph node, skin, tongue, salivary glands, intestinal mucosa, and spleen showed slight variations in staining and structure.     

Maternal malnutrition in the rat: Effects on food intake and body weight

The effects of dietary protein level on food intake and body weight were examined in adult female rats during a 35-day pre-mating period and during gestation and lactation. During the pre-mating period, no differences in daily food intake were observed among rats fed a 6% casein, 8% casein or 25% casein diet. However, during this period, rats fed the 6% casein diet gained significantly less weight than those with ad lib access to the 8% or 25% casein diets or than rats pair-fed the 25% casein diet in amounts equivalent to that consumed by rats in the 6% or 8% casein groups. Additionally, rats fed the 6% casein diet displayed decreased efficiency of energy utilization, calculated as weight gain per 100 kilocalories consumed, relative to rats fed the 8% or 25% casein diets. No differences in food intake were observed among the groups during gestation. However, rats fed the 6% casein diet gained less weight than rats fed the 8% or 25% casein diets. During lactation rats fed either the 6% or 8% casein diet consumed significantly less food than animals given the 25% casein diet ad lib. During the second week of lactation, rats receiving ad lib access to the 25% casein diet gained weight while those receiving the 6% or 8% casein diets continued to lose weight. At parturition, body weights of pups did not differ as a function of dietary condition. However, by day 12 of life, pups whose dams had ad lib access to the 25% casein diet weighed significantly more than pups whose dams consumed the 6% or 8% casein diet or whose dams were pair-fed the 25% casein diet in amounts equivalent to those consumed by rats fed the 6% or 8% casein diet.     

Melatonin and estradiol effects on food intake, body weight, and leptin in ovariectomized rats

OBJECTIVE: The study in ovariectomized (Ovx) rats, as a model of menopausal status, of the effects of melatonin (M) and/or estradiol (E), associated or not with food restriction, on body weight (BW) and serum leptin levels. METHODS: Female SD rats (200-250 g) were Ovx and treated with E, M, E+M or its diluents. Control sham-Ovx rats were treated with E-M diluents. After 7 weeks being fed ad libitum, the animals were exposed for 7 more weeks to a 30% food restriction. We measured: food intake, BW, nocturnal and diurnal urinary excretion of sulphatoxymelatonin (aMT6s), leptin in midday and midnight blood samples, glucose, total cholesterol, LDL, HDL and triglycerides. RESULTS: Day/night rhythm of aMT6s excretion was preserved in all cases. The increase of aMT6s excretion in M-treated animals basically affected the nocturnal period. In animals fed ad libitum, E fully prevented Ovx-induced increase of BW, leptin and cholesterol. Melatonin reduced food intake and partially prevented the increase of BW and cholesterol, without changing leptin levels. Under food restriction, M was the most effective treatment in reducing BW and cholesterol. Leptin levels were similar in M, E or E+M treated rats, and lower than in untreated Ovx rats. CONCLUSIONS: Our result gives a preliminary experimental basis for a post-menopausal co-treatment with estradiol and melatonin. It could combine the effectiveness of estradiol (not modified by melatonin) with the positive effects of melatonin (improvement of sleep quality, prevention of breast cancer, etc.). The possible beneficial effects of melatonin which could justify its use, need to be demonstrated in clinical trials.     

Ovarian influences on food intake and body weight regulation in lactating rats

In the following experiments, an attempt was made to determine the role of the ovary in the control of food intake and body weight regulation during lactation. In the first study, it was found that concentrations of estradiol benzoate effective in suppressing food intake and body weight in nonlactating animals were not effective during lactation. In the second experiment, ovariectomy during lactation was shown not to produce the usual increases in food intake and body weight or change in meal patterns known to occur after ovariectomy in the nonlactating rat. These results suggested that lactating animals behave the as though functionally ovariectomized and that the removal of the ovaries is of no additional consequence. The further observation that animals nursing small litters gained weight considerably more rapidly than animals nursing large litters led to the prediction that these animals would also be more responsive to the suppressive effects of EB. In the third study, EB in concentrations which are not effective in suppressing body weight in animals nursing large litters was found to suppress body weight in mothers with small litters. However, since these animals also showed a decline in milk yield, a number of alternative interpretations of these results were considered. These results, together with data concerning levels of ovarian hormones during gestation and lactation led to the hypothesis that pregnant and lactating animals undergo an elevation in body weight set-point, similar in magnitude and quality to elevations following ovariectomy in the nonlactating animal.     

Fluoxetine-maintained obese humans: effect on food intake and body weight

The effects of fluoxetine on food intake, body weight, and mood of obese individuals was examined in a 16-week inpatient/outpatient study. Six male and eight female obese volunteers began the study (four male and five females completed all phases of the study). They lived in a residential laboratory during three one-week inpatient periods separated by a 5-week and an 8-week outpatient period. Following an initial 4-day placebo baseline, participants were maintained on fluoxetine (60 mg/day) for the remainder of the study. Food intake parameters (total daily energy intake, macronutrient intake, mean number of eating bouts, interbout interval), body weight, subjective effects, and task performance were measured several times during the day during inpatient periods; food intake questionnaires were completed daily during the outpatient periods. Fluoxetine significantly reduced daily energy intake derived from fat, carbohydrate, and protein by decreasing the mean number of eating bouts per day throughout the study. No other food intake parameter was affected. Body weight was significantly reduced after 7 weeks, but not after 16 weeks of daily fluoxetine administration. These results indicate that fluoxetine reduced food intake for at least 16 weeks in nondepressed obese individuals without specifically affecting carbohydrate intake. Weight that was lost during the first few weeks of daily fluoxetine administration was subsequently regained even though food intake remained reduced. Therefore, fluoxetine maintenance does not appear promising as a sole long-term therapy for obesity.     

Exogenously administered leptin leads to weight loss and increased physical activity in the marsupial Sminthopsis crassicaudata

The adipose tissue derived cytokine leptin, modifies energy balance via effects on both food intake and energy expenditure. It is not clear, however, whether the component of energy expenditure accounted for by voluntary (nonexercise) physical activity is increased in response to leptin. The aim of this study was to investigate the effect of exogenously administered leptin on physical activity in the marsupial Sminthopsis crassicaudata. Body weight, tail width and food intake, were measured daily and physical activity was measured hourly in normal lean S. crassicaudata (n=8) with ad libitum access to standard laboratory diet. After 5 days baseline the animals were divided into two equal groups (n=4), and either human recombinant leptin (2.5 mg/kg) or placebo was administered twice daily intraperitoneally. Approximately 81% of the total daily activity during the baseline period occurred during the nocturnal phase. After 9 days of leptin administration, there were significant decreases in body weight (P<0.001) and fat content (P<0.01), which were not accompanied by a decrease in total energy intake. Overall daily physical activity increased (P=0.028); this effect was confined to the dark phase (P=0.033). We conclude that in lean S. crassicaudata the exogenous administration of human recombinant leptin results in a decrease in adiposity which occurs in the absence of a measurable effect on food intake and is associated with an increase in non-exercise physical activity at least over the duration of this study.     

Long term effects of quinine on food intake and body weight in the rat

Adulteration of a chow diet with 0.75% quinine sulfate produces a short-lived decrement in food intake in both ad lib-fed and previously food-restricted adult female rats. In contrast, quinine produces a long-lasting depression in body weight; ad lib access to quinine-treated chow results in a plateauing of body weight at a lower level until quinine is removed from the diet, despite recovery of food intake.     

Taste preferences, body weight gain, food and fluid intake in singly or group-housed rats.

Two behavioral experiments were performed to determine if the housing conditions modify taste preferences, body weight gain, food and fluid intake, and alimentary diurnal pattern in adult male rats. In Experiment 1, a two-bottle 24-h preference test (salt, sweet, sour, bitter solutions versus deionized water) was performed in singly, dually or multiply housed rats. In Experiment 2, the same sapid solutions as Experiment 1 and water were contemporaneously offered to singly, dually, or multiply housed rats. Crowded rats drank more water, sweet solution, and total fluid, but less salt solution than singly or dually housed rats during dark and whole-day periods. All rats preferred sour solution, but not bitter solution, to water. In both experiments, crowded rats gained less body weight and ate less food than dually or isolated rats. These results suggest that the housing conditions influence taste preferences, food and fluid intake, body weight gain, but not alimentary diurnal pattern in rats. An important implication of these results is that in experiments in which appetite and taste are dependent variables, all rats should be housed under the same social and environmental conditions.     

Effects of dietary sugar and of dietary fat on food intake and body fat content in rats

The long term ingestion of a sugar-rich diet (low fat) caused severe obesity in adult rats. In a separate experiment, the habitual consumption of a fat-rich diet (40% kcal from fat) also caused severe obesity. Severe obesity developed in both groups of animals even though they did not overeat. Voluntary food intake for the sugar-fed rats averaged 28,314 +/- 756 calories/rat per 55 wks which was similar to the value of 28,884 +/- 953 calories/rat per 55 wks for the fat-fed rats. However, both values were lower than that of 32,869 +/- 588 for the control rats eating Purina chow. Despite a lower caloric intake, carcass fat averaged 45 +/- 1% for rats eating the sugar-rich diet and 46 +/- 2% for rats eating the fat-rich diet, but only 33 +/- 2% for rats eating a diet of Purina chow. These results provide evidence that severe obesity can develop in the absence of hyperphagia in animals eating a sugar-rich or fat-rich diet. Finally, a rat model for severe obesity is presented in which carcass fat ranged from 18% (lean) to 61% (severe obesity) using dietary intervention alone at critical stages of the animal's life.