Suppression of food intake, body weight, and body fat by jejunal fatty acid infusions

Three experiments investigated effects of jejunal lipid infusions given on 4 or 21 consecutive days in adult, male Sprague-Dawley rats. In experiment 1, 7-h infusions of linoleic or oleic acid (0.2 ml/h for 7 h; total load = 11.5 kcal) on 4 consecutive days reduced total intake (ad libitum consumption of the liquid diet Boost, Mead Johnson, plus load) by approximately 15% and decreased weight gain compared with 4-day tests with saline administration. In experiment 2, linoleic acid at 0.1 ml/h for 7 h (5.7 kcal) was ineffective, whereas the same load delivered in 3.5 h produced effects similar in magnitude to those in the first experiment. In experiment 3, jejunal infusions of linoleic acid (0.2 ml/h for 7 h) on 21 consecutive days reduced mean total intake by 16%, body weight by 10%, and carcass fat by 48% compared with controls receiving saline. The net decrease in caloric intake may reflect the combined activation of pre- and postabsorptive mechanisms, and it suggests a possible treatment for obesity.     

Effect of intracerebroventricular angiotensin II on body weight and food intake in adult rats

We recently reported that intracerebroventricular infusions of ANG II decreased food intake and increased energy expenditure in young rats. The aim of the present study was to determine if intracerebroventricular ANG II has similar effects in adult rats. The time course of the effect was also investigated with the idea that at earlier time points, a potential role for increased hypothalamic expression of corticotropin-releasing hormone (CRH) in the anorexia could be established. Finally, the contribution of ANG II-induced water drinking to the decrease in food intake was directly investigated. Rats received intracerebroventricular saline or ANG II using osmotic minipumps. Food intake, water intake, and body weight were measured daily. Experiments were terminated 2, 5, or 11 days after the beginning of the infusions. ANG II (approximately 32 ng.kg(-1).min(-1)) produced a transient decrease in food intake that lasted for 4-5 days although body weight continued to be decreased for the entire experiment most likely due to increased energy expenditure as evidenced by increased uncoupling protein-1 mRNA expression in brown adipose tissue. At 11 and 5 days, the expression of CRH mRNA was decreased. At 2 days, CRH expression was not suppressed even though body weight was decreased. The decrease in food intake and body weight was identical whether or not rats were allowed to increase water consumption. These data suggest that in adult rats ANG II acts within the brain to affect food intake and energy expenditure in a manner that is not related to water intake.     

Effect of total colectomy and PYY infusion on food intake and body weight in rats

PYY (3-36) is postulated to act as a satiety factor in the gut-hypothalamic pathway to inhibit food intake and body weight gain in humans and rodent models. We determined the effect of 14-day continuous intravenous infusion of PYY (3-36) (175 microg/kg/day) on food intake and body weight gain in colectomized male Wistar rats. Colectomy caused an increase in plasma PYY levels at 7 days which was reduced at 14 days but still significantly elevated compared to basal preoperative values. Animals treated with continuous PYY (3-36) infusion had significantly elevated PYY levels compared to the control group throughout the whole experiment, but showed a similar pattern of food intake and body weight gain. In conclusion, although continuous intravenous infusion is the most physiologically relevant method to mimic high postprandial PYY levels, we did not observe any significant effect on food intake and body weight gain in non-food deprived colectomized animals. This suggests that PYY has, if at all, only a minor role in food intake in rats.     

Effect of cigarette smoke on body weight, food intake and reproductive organs in adult albino rats

One hour daily exposure to cigarette smoke for two months significantly decreased the body weight and food intake in male and female albino rats. The latency for conception increased significantly and the litter size decreased. Mortality rate per litter increased and grayish discoloration of the skin in the experimental group was the only congenital anomaly seen. Testes and ovaries showed a significant decrease in weight. The stroma of the ovaries were occupied by very few Graafian follicles. Testes showed disruption of the normal orderly progression of the spermatogonia. The tubules showed only one layer of spermatogonia and very few germinal cells. The number of sperms was less in the testes. The results show that exposure to cigarette smoke is detrimental to the reproductivity in both, male and female albino rats.     

Effect of hypoxic hypoxia and carbon monoxide on food intake, water intake, and body weight in two strains of rats

Two different strains of rats were exposed for 24 hours to three levels of hypoxic hypoxia: 16% oxygen, 14% oxygen, and 10% oxygen, and three levels of carbon monoxide: 250 ppm, 500 ppm, and 1000 ppm. Both strains of rats showed decreases in food intake, water intake, and weight gain that were directly related to the degree of hypoxia or carbon monoxide exposure. These results demonstrate the importance of considering nutritional alterations in biochemical studies of prolonged exposure to hypoxia or carbon monoxide.     

Effect of photoperiod on body weight and food intake of obese and lean Zucker rats

Although the rat is usually not considered to be sensitive to photoperiod, under some experimental conditions photoperiod responses are unmasked. In addition, we have observed photoperiod-induced changes in body weight gain in lean and obese Zucker rats. In this experiment, body mass, food intake, body composition, brown adipose tissue (BAT) thermogenic state, and blood concentrations of corticosterone, insulin, and glucose were evaluated under one of two lighting conditions: a short (10 h light: 14 h dark) or a long (14 h light: 10 h dark) photoperiod. Plasma corticosterone and glucose concentrations measured under fasting conditions were unaffected by photoperiod in either genotype. The amount of BAT mitochondrial protein isolated was less in long photoperiod rats. BAT mitochondrial GDP binding was unaffected by photoperiod in the lean rats, but tended to be lower in long photoperiod obese rats than in short photoperiod obese rats. Although, photoperiod had no effect on daily food intake of rats exposed to the short versus long photoperiod, body mass was heaviest in obese rats raised in long photoperiod. Plasma insulin was increased in both lean and obese rats in long photoperiod. In addition, fat storage appeared to shift to internal depots in the lean rats exposed to long photoperiod. Our data demonstrate that photoperiod does have an effect on male Zucker rats with respect to body weight and fat distribution, with the obese rats being more sensitive to changes in photoperiod than the lean rats.     

Effect of increased dietary calcium on body weight, food and water intake in oral contraceptive treated female rats

The effects of high calcium diet on body weight in OC treated rats are unknown. This study therefore investigated the effect of increasing dietary calcium from 0.9% to 2.5% on body weight, food ingestion, water intake, heart weight index and renal weight index in female Sprague-Dawley rats treated with a combination of OC steroids (ethinyloestradiol + norgestrel). The rats were assigned into three groups of average of 11 rats each; control, OC-treated and OC + Calcium – treated groups and administered orally for 10 weeks. Food and water intake, body weight, cardiac weight index, left ventricular weight index, renal weight index and serum calcium level were determined. The result shows that OC treated rats had significantly lower serum calcium concentration, body weight gain, food, water and calcium intake than those of the control rats. The OC + Calcium – treated rat had significantly higher serum calcium concentration, food, water and calcium intake but significantly lower body weight than those of the OC - treated rats. OC + Calcium - treated rats had significantly higher water intake, calcium intake and significantly lower body weight and food intake when compared with the control rats. Cardiac weight index and renal weight index was comparable in all groups. In conclusion, combined OC-induced reduction in weight gain might be associated with inhibition of the feeding center and consequent inhibition of the thirst center. Co-administration of dietary calcium augmented the reduction in weight gain seen in OC-treated rats probably by further suppression of the feeding and thirst centers.     

Suppression of food intake and body weight gain by naloxone in rats

The effect of acute and chronic administration of naloxone on food acquisition and weight gain in rats was studied in 3 experiments. One injection of a sparingly-soluble salt of naloxone in slow-release vehicle markedly lowered mean food intake over that of control rats injected with the vehicle only. Mean body weight of the naloxone-injected rats was significantly lower than that of the control group for one week.Repeated evening injections (2000 h) of naloxone hydrochloride in saline tended to reduce the night-time feeding below control levels throughout the 10-day period of naloxone administration. Food intake was significantly lower in the 4- and 8-h periods after the first injection of naloxone than that on the preceding saline control night. The initial decreases were offset by increased day-time feeding so that total daily food intake was not significantly altered over the 10 days. When saline was substituted for naloxone, food intake increased.Rats given naloxone following 24 h of fasting consumed significantly less food and gained less weight during 4 h of access to food compared to those receiving saline. After a 48-h fast naloxone-treated rats also gained significantly less body weight than those given saline, but the reduction in food intake was not statistically significant. These results suggest the possibility that endorphins may have a modulating effect on feeding activity.     

Effect of magnetic field on food and water intake and body weight of spinal cord injured rats

Chronic (2 h/d x 8 weeks) exposure to magnetic field (MF; 50 Hz, 17.9 microT) in complete spinal cord (T13) transected rats restored food intake (FI), water intake (WI) and body weight (BW) which were decreased in the spinal cord injured rats. The results suggest a significant beneficial effect of chronic exposure to magnetic field of paraplegic rats.     

Role of food intake in estradiol-induced body weight changes in female rats

In two experiments, we examined the relationship between estradiol-induced undereating and body weight loss in ovariectomized (OVX) rats. In the first experiment, both estradiol benzoate (EB) and the nonsteroidal anti-estrogen, MER-25, produced body weight losses that could not be duplicated simply by pair-feeding. In the second experiment, we compared the effects of EB treatments in obese OVX rats and in OVX rats in which the post-OVX obesity was prevented by food restriction. When fed ad libitum, both groups of oil-treated OVX rats exhibited substantial body weight gains that were not accompanied by overeating. In lean OVX rats, EB treatments caused a transient hypophagia but did not reduce body weight. These results suggest three conclusions. (1) Changes in food intake are neither necessary nor sufficient to cause some of the body weight changes induced by ovarian hormones. (2) Estradiol can depress food intake in female rats without altering the regulated body weight. (3) More attention should be paid to metabolic factors when studying gonadal influences on body weight.     

Effect of serum estradiol and leptin levels on thyroid function, food intake and body weight gain in female Wistar rats

We evaluated the interplay among estrogen, leptin and thyroid function in the regulation of body mass in female rats. Adult female rats were divided into four groups: control (C, sham-operated), ovariectomized (OVX), ovariectomized treated with estradiol benzoate (Eb) 0.7 or 14 μg/100 g bw per day, during 21 days. OVX led to an increase in body mass, food intake and food efficiency (change in body mass as function of the amount of food ingested) which were normalized by the lower Eb dose, and decreased significantly when the higher dose was given. Serum leptin levels were increased more than two-fold in all ovariectomized groups. Serum T4 levels of the Eb treated OVX were significantly lower than in the controls. Serum T3 and TSH were unaffected by OVX or by Eb treatment. Uterine type 2 iodothyronine deiodinase (D2) activity changed in parallel with serum estradiol: decreased after OVX, returned to control levels after the lower E2 treatment, and increased significantly after the high Eb dosage. The hypothalamic D2 activity was reduced around 30% in all castrated groups, treated or not with estrogen, whereas in the brown adipose tissue the enzyme was not changed. Interestingly, although estrogen-treated OVX rats had lower body weight, serum leptin was high, suggesting that estrogen increases leptin secretion. Our results show that estradiol is necessary for the hypothalamic action of leptin, since the increase in leptin levels observed in all ovariectomized rats was associated with a decrease in food intake and food efficiency only in the rats treated with estrogen.     

Pharmacological stimulation of brain carnitine palmitoyl-transferase-1 decreases food intake and body weight

Inhibition of brain carnitine palmitoyl-transferase-1 (CPT-1) is reported to decrease food intake and body weight in rats. Yet, the fatty acid synthase (FAS) inhibitor and CPT-1 stimulator C75 produces hypophagia and weight loss when given to rodents intracerebroventricularly (icv). Thus roles and relative contributions of altered brain CPT-1 activity and fatty acid oxidation in these phenomena remain unclarified. We administered compounds that target FAS or CPT-1 to mice by single icv bolus and examined acute and prolonged effects on feeding and body weight. C75 decreased food intake rapidly and potently at all doses (1-56 nmol) and dose dependently inhibited intake on day 1. Dose-dependent weight loss on day 1 persisted through 4 days of postinjection monitoring. The FAS inhibitor cerulenin produced dose-dependent (560 nmol) hypophagia for 1 day, weight loss for 2 days, and weight regain to vehicle control by day 3. The CPT-1 inhibitor etomoxir (32, 320 nmol) did not alter overall day 1 feeding. However, etomoxir attenuated the hypophagia produced by C75, indicating that CPT-1 stimulation is important for C75's effect. A novel compound, C89b, was characterized in vitro as a selective stimulator of CPT-1 that does not affect fatty acid synthesis. C89b (100, 320 nmol) decreased feeding in mice for 3 days and produced persistent weight loss for 6 days without producing conditioned taste aversion. Similarly, intraperitoneal administration decreased feeding and body weight without producing conditioned taste aversion. These results suggest a role for brain CPT-1 in the regulation of energy balance and implicate CPT-1 stimulation as a pharmacological approach to weight loss.     

Effects of beta-chlornaltrexamine on food intake, body weight and opioid-induced feeding

beta-Chlornaltrexamine (beta-CNA) is a non-equilibrium opioid receptor antagonist which alkylates and inactivates opioid receptors. Because opioid peptides are thought to contribute to the regulation of food intake, we examined the effects of intracerebroventricular (icv) injections of beta-CNA on the food intake and body weight of male rats. We also tested the ability of beta-CNA to block food intake stimulated by selective agonists of kappa, mu and delta opioid receptors: dynorphin A2 (DYN), Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAGO), and [(D-Ser2,Leu5]-enkephalin-Thr6 (DSLET). Treatment with beta-CNA caused a long-term (2-4 days) reduction in daily food intake and a concomitant reduction in body weight. An additional experiment indicated that the weight loss after beta-CNA treatment could be completely accounted for by the reduction in intake. beta-CNA treatment also abolished or greatly attenuated the feeding effects of DAGO, DSLET and DYN, even when these peptides were tested 26 hours after beta-CNA administration. The long duration of the effects of beta-CNA suggests that this compound will be a useful pharmacological tool in further study of the opioid feeding system.     

Effects of artificial sweeteners on body weight, food and drink intake

Artificial sweeteners are widely used all over the world. They may assist in weight management, prevention of dental caries, control of blood glucose of diabetics, and also can be used to replace sugar in foods. In the animal experimentation mice were given oral doses of water solutions of table top artificial sweeteners (saccharin, cyclamate based, acesulfame-K based, and aspartame) the amount of maximum Acceptable Daily Intake (ADI) ad libitum. The controls received only tap water with the same drinking conditions as the treated groups. The mice were fed chow ad libitum.We measured food intake and body weight once a week, water and solutions of artificial sweeteners intake twice a week. The data were analysed by statistical methods (T-probe, regression analysis).Consumption of sweeteners resulted in significantly increased body weight; however, the food intake did not change.These results question the effect of non-caloric artificial sweeteners on weight-maintenance or body weight decrease.     

Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats

Many antipsychotics cause weight gain in humans, but usually not in rats, when injected once or twice daily. Since blood antipsychotic half-lives are short in rats, compared to humans, chronic administration by constant infusion may be necessary to see consistent weight gain in rats. Male and female rats were implanted with mini-pumps for constant infusion of olanzapine (5 mg/kg/day), clozapine (10 mg/kg/day) or vehicle for 11 days. Food intake and body weight were measured; blood drug levels were measured by HPLC. Olanzapine increased food intake and body weight in female, but not male rats. Serum olanzapine concentrations were 30-35 ng/ml. Clozapine had no effect on food intake or body weight in female or male rats. Serum clozapine concentrations were about 75 ng/ml. Single-dose pharmacokinetic analysis revealed a serum terminal half-life of 1.2-1.5 h for each drug, with no sex differences. Despite the fact that olanzapine and clozapine promote weight gain in humans, these drugs appear to have minimal effects on body weight and food intake in rats, except for a modest effect of olanzapine in female rats, even though therapeutic levels of olanzapine are achieved in serum during chronic infusion. Hence, the rapid clearance of drug following single administration in previous studies cannot explain the weak or absent effects of antipsychotics on weight gain in this species. The rat thus appears to be an inadequate model of weight gain produced by some antipsychotics in humans.     

Accurate measurement of body weight and food intake in environmentally enriched male Wistar rats

Laboratory animals are crucial in the study of energy homeostasis. In particular, rats are used to study alterations in food intake and body weight. To accurately record food intake or energy expenditure it is necessary to house rats individually, which can be stressful for social animals. Environmental enrichment may reduce stress and improve welfare in laboratory rodents. However, the effect of environmental enrichment on food intake and thus experimental outcome is unknown. We aimed to determine the effect of environmental enrichment on food intake, body weight, behavior and fecal and plasma stress hormones in male Wistar rats. Singly housed 5–7‐week‐old male rats were given either no environmental enrichment, chew sticks, a plastic tube of 67 mm internal diameter, or both chew sticks and a tube. No differences in body weight or food intake were seen over a 7‐day period. Importantly, the refeeding response following a 24‐h fast was unaffected by environmental enrichment. Rearing, a behavior often associated with stress, was significantly reduced in all enriched groups compared to controls. There was a significant increase in fecal immunoglobulin A (IgA) in animals housed with both forms of enrichment compared to controls at the termination of the study, suggesting enrichment reduces hypothalamo‐pituitary‐adrenal (HPA) axis activity in singly housed rats. In summary, environmental enrichment does not influence body weight and food intake in singly housed male Wistar rats and may therefore be used to refine the living conditions of animals used in the study of energy homeostasis without compromising experimental outcome.     

Acute and subchronic influences of tetrahydrocannabinols on water and food intake, body weight, and temperature in rats.

Experiment 1. The acute effects of delta9-THC (1.25, 2.50, 5.00, and 10.00 mg/kg) and delta8-THC (1.25, 2.50, 5.00, and 10.00 mg/kg) was an approximately equipotent, dose related depression of water intake in water-deprived rats. Animals given hashish, inhaled as smoke, showed a depression of water consumption comparable to rats given the highest dose of either of the synthetic THCs. Water intake after chevril smoke was similar to that seen after vehicle injections. Experiment 2. A dose related depression of water-and-food intake, and reduction of body weight with a gradual recovery was found in rats, maintained on a Limited Time of drinking schedule (LT, 2 hr) and subchronically (21 days) treated with delta9-THC (1.25, 2.50, or 5.00 mg/kg). From the 22nd day all animals were given the vehicle only for 10 days. There were no indications of withdrawal effects due to the drug termination. Reinstating the drug after the 10 day drug free period suggested an increased sensitivity to THC as compared to the 21st injection. Experiment 3. In non-deprived rats delta9-THC caused similar effect as in Exp. 2, although to less extent. From both experiments it is concluded that there is an inhibition or even loss of body weight and that food intake seems more severely depressed than water intake. The temperature recordings suggest that the predominant consequence of lower, behaviorally, effective doses of THC on rectal temperature of rats is hyperthermia rather than hypothermia. Initially this effect was most pronounced for the lowest dose (1.25 mg/kg) but with repeated injections the two higher doses (2.50 and 5.00 mg/kg) showed hyperthermia to the same extent as the lowest dose. Hypothermia was seen after a high dose of delta8-THC (20.00 mg/kg) but after 3 daily injections this effect was gone.     

Acute activation of ER alpha decreases food intake, meal size, and body weight in ovariectomized rats

Estradiol exerts many of its actions by coupling with two nuclear estrogen receptor (ER) proteins, ER alpha, and ER beta. While the acute, anorexigenic effect of estradiol appears to involve such a mechanism, the relative contributions of ERalpha and ERbeta are equivocal. To address this problem, food intake was monitored in ovariectomized (OVX) rats following acute administration of a selective ER alpha agonist (4,4',4'-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol, PPT; dose range = 0-200 microg), a selective ER beta agonist (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN; dose range = 0-600 microg), and a physiological (4 microg) dose of estradiol benzoate (EB). While PPT-treated rats displayed dose-dependent decreases in daily food intake and body weight, neither of these measures was influenced by any dose of DPN. In addition, DPN failed to modulate the anorexigenic effect of PPT when the two ER agonists were coadministered. Meal pattern analysis revealed that the anorexigenic effect of 75 microg PPT (a dose of PPT that produced a similar decrease in daily food intake as 4 microg EB) was mediated by a decrease in meal size, not meal number. Thus, PPT, like EB and endogenous estradiol, decreases food intake by selectively affecting the controls of meal size. The finding that acute administration of 75 microg PPT failed to induce a conditioned taste aversion suggests that the anorexigenic effect of this dose of PPT is not secondary to malaise. Taken together, our findings demonstrate that selective activation of ER alpha decreases food intake, body weight, and meal size in the ovariectomized rat.