Effects of cigarette smoke and nicotine on feeding and energy

Much evidence has accumulated indicating that cigarette smokers weigh less than non-smokers and that smokers gain weight when they cease smoking. In the present study we evaluated the effects of cigarette smoke and nicotine on food intake, weight gain, resting energy output, brown fat mass and opiate binding (opiates initiate feeding in sated rats) in rats. Chronic smoke exposure slightly suppressed growth rate and food intake after 14 days of smoke exposure. Blood glucose levels and intrascapular brown adipose mase were increased as a result of smoke exposure. Hamsters chronically exposed to cigarette smoke decreased body weight; however, food intake was not significantly suppressed. Short term (5 day) exposure to nicotine (4 and 2 mg/kg/day) suppressed growth rate and food intake. Nicotine (4 and 2 mg/kg) significantly suppressed water ingestion in water-deprived rats and altered the quantities of flavored solutions ingested by rats compared with those ingested by rats receiving no nicotine. Thus cigarette smoke and nicotine exposure affects food intake, energy utilization and taste perception; all parameters which contribute to overall body mass; however, these parameters change in a complex manner with only small changes occurring at specific time intervals.     

Influence of glucose, medium- and long-chain triglyceride gastric loads and forced exercise on food intake and body weight in rats

The purpose of this study was to examine the effect of oesophageal loads of glucose, medium (MCT)-and long-chain (LCT) triglycerides, plus treadmill exercise on food intake and body weight in rats. On test days, male rats were administered a gastric aqueous solution of glucose, MCT, LCT or water via an oesophageal tube. One hour later, the animals were forced to run on a treadmill for two hours at a speed of 20 m/min at 0% grade. At the beginning of the 12-hour dark cycle (at 7 p.m.) runners were returned to their cages. On control days, the same gastric loads were administered, but the animals remained in their cages. Food intake was continuously measured during both the dark and light periods. A reduction in body weight and total food intake was found after exercise. The food intake suppressing effect of exercise was seen in the first hours of the dark period. Following MCT and LCT oil stomach loads FI decrease was comparable but the latency of the effect varied. Stomach loads of MCT oil induced a reduction in FI within the 0-3 h of food availability whereas LCT oil suppressed intake during the 3-6-h dark period. This could be explained by their different metabolite fate.     

Effects of selective estrogen receptor agonists on food intake and body weight gain in rats

Ovariectomized (OVX) rats eat more and gain weight more rapidly than sham-operated (SO) rats and estradiol (E(2)) treatment attenuates food intake and body weight gain in OVX rats. Studies were designed to test the hypothesis that the alpha subtype of the estrogen receptor (ERalpha) mediates the attenuating effects of E(2) on food intake and body weight gain while the beta subtype (ERbeta) mediates opposing actions that lead to increased food intake and body weight gain. Female rats were SO or OVX and treated daily with vehicle (dimethylsulfoxide, DMSO) or E(2) (10 microg/day), or the ERalpha-selective agonist, 4,4',4'-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, 0.5 mg/day), or the ERbeta-selective agonist, 2,3-bis(4-hyroxyphenyl)-propionitrile (DPN, 0.5 mg/day) for 14 days. Total food intake was significantly reduced by E(2) and PPT, but not DPN. Total body weight gain was significantly increased in OVX rats compared to SO rats and treatment with E(2) or PPT, but not DPN, significantly decreased total body weight gain to levels that were not significantly different from SO rats. A dose-response study of PPT indicated that at 0.25 mg/day, PPT significantly reduced total 21-day food intake and body weight gain and, at 0.13 and 0.06 mg/day, PPT significantly reduced total body weight gain compared to OVX rats without significantly reducing total food intake. A dose-response study of DPN indicated that none of the three doses of DPN significantly altered total 21-day food intake or total body weight gain. These results suggest ERalpha mediates the attenuating effects of estrogens on food intake and body weight gain while ERbeta has no effect on these variables.     

Feeding inhibition and death produced by glucose ingestion in the rat

The ingestion of a 7% or 8% glucose solution by normal rats maintained on a one hr/day feeding schedule significantly suppressed food intake and body weight, and resulted in death. A 3.5% glucose solution did not have these effects, while a 21% glucose solution resulted in greater feeding and weight suppression, but no fatalities. The addition of saccharin to the glucose solutions enhanced their suppressive effects, although saccharin by itself did not reduce food intake or body weight. The results indicate that caloric depletion is not the sole cause of glucose-induced death, and some other factor(s), perhaps insulin hypersecretion, must also be responsible for this unusual effect.     

Naloxone suppression of food and water intake and cholecystokinin reduction of feeding is attenuated in weanling rats with dorsomedial hypothalamic lesions

In Experiment 1, sham operated (SCON) and dorsomedial hypothalamic nuclei (DMN) lesioned (L) rats were given saline or naloxone (0.1, 1.0 or 2.0 mg/kg) just prior to the onset of the dark cycle, lights out. Compared to saline injections, naloxone at all doses suppressed the cumulative food intake of the SCON during the second and third hr of measurement. Naloxone was without significant effect on the food intake of DMNL rats. Similar results were obtained in Experiment 2, except that naloxone at 2.0 mg/kg significantly suppressed the DMNL rats' food intake by the fourth hr of measurement. Cumulative water intake of both groups was significantly suppressed by naloxone in both experiments but its effects appeared to be attenuated in the DMNL group. In a preliminary trial cholecystokinin octapeptide (3.0 and 6.0 micrograms/kg) given at the onset of the dark cycle significantly suppressed the food intake of the SCON group but had no significant effect on the DMNL rats. The possibility exists that the reduced food intake and lower body weight of DMNL rats may partially result from damage to an opioid system. The data also tentatively suggest that DMN may play a role in cholecystokinin-induced satiety.     

Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors

Cannabidiol (CBD) is a major non-psychotropic constituent of Cannabis sativa, with well recognized therapeutic potential. Considering the importance of the endogenous cannabinoid system to the regulation of food intake and energy balance we studied the effects of repeated CBD administration on body weight gains in rats. Male Wistar rats (260 ± 20 g at start of study) received intraperitoneal injections of CBD at doses of 2.5 and 5mg/kg/day for 14 consecutive days and body weight gains were monitored. Both doses of CBD produced significant decrease in body weight gain, with the effect produced by 5mg/kg being more pronounced. The CB2 receptor selective antagonist, AM630, blocked the decrease in body weight gain. AM630 alone did not affect body weight gain. The results suggest that CBD has the ability to alter body weight gain, possibly via the CB2 receptor. CB2 receptors may play a role in the regulation of body weight and the effects of CB2 specific ligands should be further investigated in studies of body weight regulation.     

Systemic nicotine alters whole-body fat utilization in female rats

Cigarette smoking produces weight suppression in humans that often rebounds following smoking cessation. Nicotine (NIC) administration produces similar effects in rats. While changes in food intake are thought to account for some of the body weight changes, few reports have investigated how NIC affects whole-body metabolism. In the present study, measures of respiratory quotient (RQ) and energy expenditure (EE) were used to investigate metabolic changes that may contribute to NIC's effects on body weight. Female rats (n=46) were implanted for 14 days with subcutaneous Alzet minipumps containing NIC (6 mg/kg/day) or its vehicle. One-hour metabolic test sessions occurred four times: 2 and 12 days after pump implant and 2 and 8 days after pump removal. NIC initially suppressed body weight gain, followed by steady recovery that was briefly exaggerated after withdrawing NIC. Daily food intake was acutely suppressed by NIC and acutely potentiated after NIC cessation. RQ, but not EE, was suppressed by NIC 2 days after pump implant indicating increased fat utilization. Conversely, RQ was increased 2 days after pump removal signaling increased fat storage. These findings indicate that acute changes in whole-body metabolism may contribute to the weight modulating effects of NIC.     

Effects of short-term and prolonged infusions of somatostatin on endocrine pancreas, body weight and food intake in rats

Infusion of cyclic somatostatin (700 mg/kg/min) for 4 h in rat fed and libitum suppressed basal insulin but not glucagon release. It was accompanied by hypoglycemia during the first hour whereas, at the end of the infusion, hyperglycemia was present. The same dose of somatostatin applied 60 min prior to and during a 30 min load of glucose or arginine significantly inhibited their effects on insulin and glucagon release. In contrast, when this dose of somatostatin was given during a 24 h period by the i.v. route it did not inhibit glucose induced insulin release though circulating somatostatin levels were constantly and markedly elevated. Furthermore, in rats continuously infused with somatostatin for 4 days, no effect was found either on plasma concentrations of glucose, insulin, glucagon, growth hormone and cyclic AMP, or on body weight gain, food consumption or water intake. The pancreases of these animals showed normal concentrations of insulin and glucagon and a normal nuclear area of D-cells. Our experiments demonstrate that, in short-term experiments in rats, somatostatin influences insulin and glucagon release as well as glucose homeostasis. Furthermore, they suggest that during prolonged i.v. administration of somatostatin, rats develop mechanisms counteracting the effect of the peptide, e.g., peripheral tachyphylaxis.     

Role of the hippocampus in the sex-dependent regulation of eating behavior: studies with kainic acid

Marked hyperphagia with an increase in the rate of body weight gain was noted in adult female rats 4 days after injections of 2 nmoles of kainic acid into the dorsal and ventral parts of hippocampus. The effect was still present 70 days later. At this time the increase in daily food intake and body weight gain amounted, respectively, to 39% and 93% over the control value. There was no change in water intake. The injection of kainic acid into only one part of the hippocampus--either dorsal or ventral--did not induce hyperphagia. Male rats with kainic acid lesion did not show changes in food intake or body weight gain as compared to vehicle-treated controls. In both sexes the degeneration of hippocampal perikarya induced by kainic acid was associated with a 50-60% decrease in glutamic acid decarboxylase activity and [3H]glutamate uptake, as well as with a small decrease in [3H]glutamate uptake in the hypothalamus, an area that receives glutamatergic fibers from the hippocampus. The results show that the hippocampus appears to play an important role in appetite motivation control by a mechanism which is sex-related.     

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.     

Elevated blood glucose levels and satiety in the rat.

Thirteen rats were placed on a feeding schedule of two 3 hr periods of food availability daily. blood glucose levels of the experimental animals were altered by intraperitoneal injection of 8 ml of 2, 5, 8, 12, 16, 20 and 25 percent glucose solutions and by intragastric loading of 8 ml of 25, 50 and 65 percent glucose solutions in 10 different feeding experiments. In 4 additional experiments, experimental animals received intraperitoneal injections of 8 ml of 12, 16, 20 and 25 percent solutions of mannitol, a non-metabolizable sugar-alcohol. Controls always received identical quantities of mammalian Ringer's solution administered via the same route as in the experimentals. Another set of 20 rats was used to determine glucose tolerance curves for each concentration of glucose and mannitol administered. No food intake depression occurred following intraperitoneal injections of 2, 5, 8 and 12 percent glucose, 12 percent mannitol and following intragastric loading of 25, 50 and 65 percent glucose. However, intraperitoneal injections of 16, 20 and 25 percent glucose and mannitol caused depression of food intake. No depression of food intake occurred following intragastric loading of 50 and 65 percent glucose solutions which raised blood glucose levels a minimum of 43 mg percent and 55 mg percent above basal, respectively, for the duration of the 3 hr feeding period. These minimum blood glucose levels greatly exceed normal values following a meal. It was concluded that blood glucose level per se is not an important feedback parameter in the long-term control of food intake, and the depression in food intake following intraperitoneal injections of 16, 20 and 25 percent glucose and mannitol solutions was due to an abnormal physiological condition.     

Subdiaphragmatic vagal deafferentation fails to block the anorectic effect of hydroxycitrate

We investigated the neural mediation of the feeding suppression through orally administered hydroxycitrate (HCA) in male rats that were fed a high-glucose diet (about 48% glucose). Ten-day ad libitum food intake and body weight regain after previous body weight loss (13% of initial body weight) due to restrictive feeding were measured in rats with sham deafferentation (SHAM; n = 6), subdiaphragmatic vagal deafferentation (SDA; n = 7), and SDA plus celiac-superior mesenteric ganglionectomy (SDA/CGX; n = 9). HCA suppressed the 10-day cumulative food intake in all surgical groups and body weight regain in SDA and SDA/CGX groups. Independent of HCA, SDA and SDA/CGX rats consumed less food and gained less weight compared to SHAM rats. These results demonstrate that all vagal afferents from below the diaphragm and vagal efferents of the dorsal trunk as well as splanchnic nerves (afferents and efferents) are not necessary for the feeding-suppressive effect of HCA in this animal model. Vagal afferents, however, appear to play a role in the control of intake when a high-glucose diet is consumed after a period of restrictive feeding.     

Effects of age and drugs on food and fluid intake.

In young adults rats (5-month-old) d-amphetamine (2 mg/kg/d), administered on a long-term basis via drinking water, caused a moderate reduction in the intake of nutriments, which in part normalized within three weeks. Self-administration of a daily dose of 20 mg per kg diazepam over a period of 26 days led neither to hypodipsia nor to anorexia. Pentylenetetrazol (70 mg/kg/d) primarily produced a hypodipsia. The three drugs did not influence body weight. In 27-month-old rats d-amphetamine and pentylenetetrazol had the same qualitative effects. Intake of nutriments and the development of body weight were influenced more strongly than in young rats. Diazepam also had a marked effect in old animals. Nootropics (piracetam, pyrithinol, hydergin, centrophenoxin, aniracetam) had no effects on the parameters observed. When the agents were given in combination in both age groups the nootropic piracetam (230 mg/kg/d) weakened the effects induced by d-amphetamine, pentylenetetrazol or diazepam alone. The benzodiazepine, however, enhanced the loss of body weight and fluid intake in old rats caused by the stimulant or analeptic, whereas food intake remained unaffected. The results support the hypothesis that an organism's adaptivity to external and internal stimuli is reduced in later life. The behavior of young and old rats in the open field was not affected by any drug medication.     

Phentolamine stimulates insulin release and glucose clearance and suppresses food ingestion

In Experiment One, phentolamine (PTA), an alpha-adrenergic blocker, was injected in rats at doses of 0, 50, 100, 200, and 300 micrograms/kg following a 4-hr fast. Measurement of food intake 1-hr postinjection revealed that 300 micrograms/kg PTA reduced food intake. Experiment Two evaluated the potential aversiveness of 300 micrograms/kg PTA. Four-hour fasted rats were adapted to a milk diet as the only food source during a 1-hr intake measurement period. After the 15-day adaptation period, three separate groups of animals (n = 8 per group) received the milk with cherry flavoring added and infections of either 1% body weight 0.9 NaCl, isosmotic LiCl or 300 micrograms/kg PTA. Only those subjects that had received LiCl injections developed a reliable aversion to the cherry-flavored milk. The final experiments subdivided the 1-hr feeding period into three 20-min segments and, in separate animals, food intake or plasma insulin and glucose changes were assessed. The animals were assigned to one of two groups receiving either 300 micrograms/kg PTA or equivolume 0.9% NaCl. PTA-injected subjects showed an immediate modest enhancement of insulin release during the first 20-min feeding segment following injection, compared to controls, while blood glucose levels decreased but never differed reliably between groups. Food intake was reliably suppressed in the second and third 20-min segments for the PTA-injected rats. We advance that PTA by enhancing glucose clearance may be reducing ingestion.     

MTII administered peripherally reduces fat without invoking apoptosis in rats

The melanocortin (MC) system in the brain is believed to be an important downstream effector of leptin signaling; interference with MC functioning results in severe obesity. Melanotan II (MTII), an MC3/4-receptor agonist, produces similar behavioral and metabolic outcomes to those observed after leptin treatments, which enhance apoptosis in specific fat depots. To determine whether MTII also mediates adipose apoptosis induced by leptin treatment, two groups of rats (n=8) received MTII (2 mg/kg, i.p.) or saline (2 ml/kg) once daily for 4 days and had free access to food and water, and a third group was injected with saline and pair-fed (PF) to MTII treated rats. Food intake, water intake, body temperature, and body weight were measured daily. MTII reduced food and water intake and body weight gain (P<.05) and decreased body temperature compared to PF and saline-treated control groups. Retroperitoneal white adipose tissue (WAT) mass and epididymal WAT mass were reduced 46.3% and 21.1%, respectively (P<.05), after MTII, but not after PF, compared with the saline control rats. Both MTII- (25.0%) and PF (33.3%)-treated rats had decreased brown fat weight (P<.05), whereas muscle mass remained unchanged. Free fatty acid concentrations in serum were not different between MTII and control groups, but increased by 56.4% in PF group. DNA fragmentation assay did not support a role for MTII as an apoptotic signal in any of the fat tissues tested. These results show that in addition to reducing food intake and inhibiting body weight gain, intraperitoneal administration of MTII reduces fat mass, most likely by accelerated lipid mobilization, but not by apoptosis.     

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.     

Long-term effects of insulin in weanling rats with dorsomedial hypothalamic hypophagia: Food intake,efficiency of food utilization,body weight and composition

Twenty-five day-old Sprague-Dawley rats received electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated rats served as controls. Two weeks after the operation the DMNL rats showed reduced (p<0.001) body weight and food intake but normal body composition (Lee Index) and efficiency of food utilization (EFU). During the following 32 days subcutaneous administration twice daily of intermediary-acting insulin in increasing doses (mean daily dose 2.64 IU/kg) caused highly significant increases in food intake in both groups. Injection for the subsequent 14 days of higher doses of insulin (mean daily dose 5.64 IU/kg) caused dramatic increase in both food intake and Lee Index and equalized the rate of weight gain with that of the controls. However, in absolute terms the DMNL rats remained consistently hypophagic and weighed significantly less than the controls. Both DMNL rats and controls showed the same EFU during both periods of insulin administration. On discontinuation of hormone treatment during the subsequent 20 days, food intake and body weight gains returned to pretreatment values and the insulin-induced increased Lee Index returned into the low-normal range. However, EFU was significantly (p<0.05) decreased during this period. At sacrifice, plasma glucose, glycerol, free fatty acids and total protein and carcass lipid and protein were normal in the DMNL rats. Absolute and relative (per 100 g body weight and per metabolic size) weight of epididymal fat pads, pituitaries, adrenals and kidneys were normal in the DMNL rats but testes weight per 100 g body weight was higher (p<0.05) in the DMNL rats. Although DMN lesions may remove some glucose-sensitive elements within the hypothalamus, the animals are still capable of responding to the food intake and weight-promoting properties of insulin, as do intact animals.     

Body weight gain, food intake and adrenal development in chronic noise stressed rats

Wistar chronic treated rats (30 days) were used to investigate the effect of hypothalamic-pituitary-adrenal activity on growth, food intake and adrenal development (weight and DNA content). The animals were submitted to noise stress, ACTH administration and dexamethasone suppression test. Noise stress decreased body weight gain and food intake. No adrenal hypertrophy was observed but an increase in relative DNA content by stress has been found. ACTH and dexamethasone treated rats showed a body weight and food intake decrease vs. controls. The effect on body weight was higher in dexamethasone treated rats. Adrenal hypertrophy and hyperplasia were found in ACTH treated rats, whereas dexamethasone provoked adrenal atrophy with a decrease in DNA content.     

Effect of crowding on some physiological and behavioral variables in adult male rats

The effect of two population densities on body weight gain, food and water intake and the weight of some organs and glands was studied in adult male rats. Behavioral reactivity to open field was also assessed. Crowded rats (10 animals per cage) showed lower body weight gain than control rats (3 per cage) throughout all the experimental period. Crowding decreased food intake and increased water intake. Any effect of crowding on the weight of thymus, liver and endocrine glands (except testes) was found. Open field defecation and activity were the same in control and crowded rats. Discrepancies from earlier works could likely be due to methodological differences and these are discussed in the text.     

Effects of abuse pattern of gestational toluene exposure on metabolism, feeding and body composition

AIMS: Inhalant abuse during pregnancy lowers birth weight and impedes early development. These studies explored the effects of brief, repeated, prenatal toluene exposures in pregnant female rats on body weight, metabolic rate, body composition, and food intake in their offspring. METHOD: Rats were exposed to 0, 8000, 12,000, or 16,000 ppm of toluene twice daily for 15 min from gestational days 8 to 20. The effects of such exposures on post-weaning litter weights, oxygen consumption, carbon dioxide output, and body fat content were determined in 2 cohorts (n=23, n=24) of offspring. Food intakes and weight changes in response to 3 different diets (regular chow, purified diet, purified high fat diet) were examined in another cohort (n=24) from postnatal days 72 to 116. RESULTS: Litter weights showed a significant linear decrease as a function of toluene dose. Offspring exposed to the 16,000 ppm toluene dose displayed statistically lower energy expenditures than control rats. Male rats exposed to 8000 or 16,000 ppm toluene had significantly greater percentage of body fat as well as total body fat than the other groups. Toluene also significantly suppressed weight gain over the time chow was consumed compared to the 0 ppm control group. Finally there were trends for a main effect of toluene dose on food intake during chow and during high fat diet consumption, with rats in the 12,000 ppm group consuming more than the 0 ppm group on both diets. DISCUSSION: These data suggest that, in addition to other previously documented abnormalities in neurological development and behavior, the physiological regulation of metabolism and body composition in males as well as food intake and weight gain in both sexes may be altered by prenatal exposure to toluene.