Influence of ghrelin on gastric and duodenal growth and expression of digestive enzymes in young mature rats.

Ghrelin, a nature ligand for the growth hormone secretagogue receptor (GHS-R), stimulates a release of growth hormone, prolactin and adrenocorticotropic hormone. Also, ghrelin increases food intake in adult rats and humans and exhibits gastroprotective effect against experimental ulcers induced by ethanol or stress. The aim of present study was to examine the influence of ghrelin administration on gastric and duodenal growth and expression of pepsin and enterokinase in young mature rats with intact or removed pituitary. METHODS: Two week after sham operation or hypophysectomy, eight week old Wistar male rats were treated with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose) i.p. twice a day for 4 days. Expression of pepsin in the stomach and enterokinase in the duodenum was evaluated by real-time PCR. RESULTS: In animals with intact pituitary, treatment with ghrelin increased food intake, body weight gain and serum level of growth hormone and insulin-like growth factor-1 (IGF-1). These effects were accompanied with stimulation of gastric and duodenal growth. It was recognized as the significant increase in gastric and duodenal weight and mucosal DNA synthesis. In both organs, ghrelin administered at the dose of 8 nmol/kg caused maximal growth-promoting effect. In contrast to these growth-promoting effects, administration of ghrelin reduced expression of mRNA for pepsin in the stomach and was without effect on expression of mRNA for enterokinase in the duodenum. Hypophysectomy alone lowered serum concentration of growth hormone under the detection limit and reduced serum level of IGF-1 by 90%. These effects were associated with reduction in daily food intake, body weight gain and gastroduodenal growth. In hypophysectomized rats, administration of ghrelin was without significant effect on food intake, body weight gain or growth of gastroduodenal mucosa. Also, serum concentration of growth hormone or IGF-1 was not affected by ghrelin administration in rats with removed pituitary. CONCLUSION: Administration of ghrelin stimulates gastric and duodenal growth in young mature rats with intact pituitary, but inhibits expression of mRNA for pepsin in the stomach. Growth hormone and insulin-like growth factor-1 play an essential role in growth-promoting effects of ghrelin in the stomach and duodenum.     

Variable effect of ghrelin administration on pancreatic development in young rats. Role of insulin-like growth factor-1.

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been primarily isolated from the human and rat stomach. Ghrelin has been shown to stimulate appetite and fat deposition in adult rats and humans. The aim of this study was to investigate the effect of ghrelin administration on pancreatic growth in suckling, weaned and peripubertal seven week old rats. Rats were treated with saline or ghrelin (4, 8 or 16 nmol/kg/dose) intraperitoneally twice a day: suckling rats were treated for 7 or 14 days starting from the first postnatal day, three week old weaned rats and seven weeks old rats were treated for 5 days. Treatment with ghrelin did not affect animal weight in suckling or weaned rats, whereas in young seven week old rats, ghrelin caused a significant increase in body weight. Ghrelin decreased food intake in weaned rats; whereas in seven week old rats, food intake was enhanced. In suckling rats, ghrelin decreased the pancreatic weight, pancreatic amylase content, DNA synthesis and DNA content. In contrast, ghrelin increased pancreatic weight, DNA synthesis, DNA content and amylase content in weaned or young seven week old rats. Pancreatic blood flow was not affected by ghrelin in any group of rats tested. Ghrelin increased serum level of growth hormone in all rats. This effect was weak in suckling rats, higher in weaned and the highest in seven week old animals. Ghrelin did not affect serum level of insulin-like growth factor-1 (IGF-1) in suckling rats. In weaned and in seven week old rats, treatment with ghrelin caused increase in serum level of IGF-1. We conclude that ghrelin reduces pancreatic growth in suckling rats; whereas in weaned and young seven week old animals, treatment with ghrelin increases pancreatic growth. This biphasic effect of ghrelin in young animals on pancreatic growth seems to be related to age-dependent changes of the release of anabolic IGF-1.     

Sibutramine alters the central mechanisms regulating the defended body weight in diet-induced obese rats

Chronic administration of sibutramine lowers body weight, presumably by altering brain monoamine metabolism. Here the effect of sibutramine on sympathoadrenal function (24-h urine norepinephrine and epinephrine levels) and arcuate nucleus (ARC) neuropeptide Y (NPY) and proopiomelanocortin (POMC) expression was assessed in diet-induced obese rats fed a low-fat diet. Chronic (10 wk) sibutramine [5 mg. kg(-1). day(-1) ip; rats fed ad libitum and injected with sibutramine (AS)] lowered body weight by 15% but only transiently (3-4 wk) reduced intake compared with vehicle-treated controls [rats fed chow ad libitum and injected with vehicle daily (AV)]. Other rats food restricted (RS) to 90% of the weight of AS rats and then given sibutramine restored their body weights to the level of AS rats when allowed libitum food intake. After reequilibration, RS rats were again energy restricted to reduce their weight to 90% of AS rats, and additional vehicle-treated rats (RV) were restricted to keep their body weights at the level of AS rats for 3 wk more. Terminally, total adipose depot weights and leptin levels paralleled body weights (AV > AS = RV > RS), although AS rats had heavier abdominal and lighter peripheral depots than RV rats of comparable body weights. Sibutramine treatment increased sympathetic activity, attenuated the increased ARC NPY, and decreased POMC mRNA levels induced by energy restriction in RV rats. Thus sibutramine lowered the defended body weight in association with compensatory changes in those central pathways involved in energy homeostasis.     

Effects of chronic food restriction and treatments with leptin or ghrelin on different reproductive parameters of male rats

The existence of a close relationship between energy status and reproductive function is well-documented, especially in females, but its underlying mechanisms remain to be fully unfolded. This study aimed to examine the effects of restriction of daily calorie intake, as well as chronic treatments with the metabolic hormones leptin and ghrelin, on the secretion of different reproductive hormones, namely pituitary gonadotropins and prolactin, as well as testosterone, in male rats. Restriction (50%) in daily food intake for 20 days significantly reduced body weight as well as plasma PRL and T levels, without affecting basal LH and FSH concentrations and testicular weight. Chronic administration of leptin to rats fed ad libitum increased plasma PRL levels and decreased circulating T, while it did not alter other hormonal parameters under analysis. In contrast, in rats subjected to 50% calorie restriction, leptin administration increased plasma T levels and reduced testis weight. Conversely, ghrelin failed to induce major hormonal changes but tended to increase testicular weight in fed animals, while repeated ghrelin injections in food-restricted males dramatically decreased plasma LH and T concentrations and reduced testis weight. In sum, we document herein the isolated and combined effects of metabolic stress (50% food restriction) and leptin or ghrelin treatments on several reproductive hormones in adult male rats. Overall, our results further stress the impact and complex way of action of different metabolic cues, such as energy status and key hormones, in reproductive function also in the male.     

Increase in hypothalamic AMPK phosphorylation induced by prolonged exposure to LPS involves ghrelin and CB1R signaling

Acute administration of lipopolysaccharide (LPS) from Gram-negative bacteria induces hypophagia. However, the repeated administration of LPS leads to desensitization of hypophagia, which is associated with increased hypothalamic p-AMPK expression. Because ghrelin and endocannabinoids modulate AMPK activity in the hypothalamus, we hypothesized that these neuromodulators play a role in the reversal of tolerance to hypophagia in rats under long-term exposure to LPS. Male Wistar rats were treated with single (1 LPS, 100 μg/kg body weight, ip) or repeated injections of LPS over 6 days (6 LPS). Food intake was reduced in the 1 LPS, but not in the 6 LPS group. 6 LPS rats showed an increased serum concentration of acylated ghrelin and reduced ghrelin receptor mRNA expression in the hypothalamus. Ghrelin injection (40 μg/kg body weight, ip) increased food intake, body weight gain, p-AMPK hypothalamic expression, neuropeptide Y (NPY) and Agouti related peptide (AgRP) mRNA expression in control animals (Saline). However, in 6 LPS rats, ghrelin did not alter these parameters. Central administration of a CB1R antagonist (AM251, 200 ng/μl in 5 μl/rat) induced hypophagia in 6 LPS animals, suggesting that the endocannabinoid system contributes to preserved food intake during LPS tolerance. In the presence of AM251, the ability of ghrelin to phosphorylate AMPK in the hypothalamus of 6 LPS group was restored, but not its orexigenic effect. Our data highlight that the orexigenic effects of ghrelin require CB1R signaling downstream of AMPK activation. Moreover, CB1R-mediated pathways contribute to the absence of hypophagia during repeated exposure to endotoxin.     

Motivation to obtain preferred foods is enhanced by ghrelin in the ventral tegmental area

Ghrelin is an orexigenic peptide that acts within the central nervous system to stimulate appetite and food intake via the growth hormone secretagogue receptor (GHS-R). It has been hypothesized that ghrelin modulates food intake in part by stimulating reward pathways in the brain and potentially stimulating the intake of palatable foods. Here we examined the effects of chronic ghrelin administration in the ventral tegmental area (VTA) via osmotic minipumps on 1) ad libitum food intake and bodyweight; 2) macronutrient preference; and 3) motivation to obtain chocolate pellets. In the first study rats receiving ghrelin into the VTA showed a dose-dependent increase in the intake of regular chow, also resulting in increased body weight gain. A second study revealed that intra-VTA delivery of the ghrelin receptor antagonist [Lys-3]-GHRP-6 selectively reduced caloric intake of high-fat chow and reduced body weight gain relative to control and ghrelin treated rats. The third study demonstrated that food restricted rats worked harder for food pellets when infused with ghrelin than when infused with vehicle or ghrelin receptor antagonist treated rats. Finally, rats trained on an FR1 schedule but returned to ad libitum during ghrelin infusion, responded at 86% of baseline levels when they were not hungry, whereas saline infused rats responded at 36% of baseline. Together, these results suggest that ghrelin acts directly on the VTA to increase preference for and motivation to obtain highly-palatable food.     

Motivation to obtain preferred foods is enhanced by ghrelin in the ventral tegmental area

Ghrelin is an orexigenic peptide that acts within the central nervous system to stimulate appetite and food intake via the growth hormone secretagogue receptor (GHS-R). It has been hypothesized that ghrelin modulates food intake in part by stimulating reward pathways in the brain and potentially stimulating the intake of palatable foods. Here we examined the effects of chronic ghrelin administration in the ventral tegmental area (VTA) via osmotic minipumps on 1) ad libitum food intake and bodyweight; 2) macronutrient preference; and 3) motivation to obtain chocolate pellets. In the first study rats receiving ghrelin into the VTA showed a dose-dependent increase in the intake of regular chow, also resulting in increased body weight gain. A second study revealed that intra-VTA delivery of the ghrelin receptor antagonist [Lys-3]-GHRP-6 selectively reduced caloric intake of high-fat chow and reduced body weight gain relative to control and ghrelin treated rats. The third study demonstrated that food restricted rats worked harder for food pellets when infused with ghrelin than when infused with vehicle or ghrelin receptor antagonist treated rats. Finally, rats trained on an FR1 schedule but returned to ad libitum during ghrelin infusion, responded at 86% of baseline levels when they were not hungry, whereas saline infused rats responded at 36% of baseline. Together, these results suggest that ghrelin acts directly on the VTA to increase preference for and motivation to obtain highly-palatable food.     

Anti-cachectic effect of ghrelin in nude mice bearing human melanoma cells

Ghrelin is a novel brain-gut peptide that stimulates food intake and body weight gain. We studied the anabolic effect of ghrelin in a cancer cachexia mouse model. SEKI, a human melanoma cell line, was inoculated into nude mice to examine the effects of ghrelin on food intake and body weight. The intraperitoneal administration of ghrelin twice a day (6 nmol/mice/day) for 6 days suppressed weight loss in SEKI-inoculated mice and increased the rate of weight gain in vehicle-treated nude mice. Ghrelin administration also increased food intake in both SEKI- and vehicle-treated mice. Both the weight of white adipose tissue and the plasma leptin concentration were reduced in tumor-inoculated mice compared with vehicle-treated mice; these factors increased following ghrelin administration. The levels of both ghrelin peptide and mRNA in the stomach were upregulated in tumor-inoculated mice. The anabolic effect of ghrelin efficiently reverses the cachexia in mice bearing SEKI human melanoma. Ghrelin therefore may have a therapeutic ability to ameliorate cancer cachexia.     

Effects of intermittent intraperitoneal infusion of salmon calcitonin on food intake and adiposity in obese rats

Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces no effect or a transient reduction in daily food intake and body weight. Our aim was to identify an intermittent dosing strategy for intraperitoneal infusion of salmon calcitonin (sCT), a homolog of amylin that produces a sustained 25-35% reduction in daily food intake and adiposity in diet-induced obese rats. Rats (649 +/- 10 g body wt, 27 +/- 1% body fat), with intraperitoneal catheters tethered to infusion swivels, had free access to a 45% fat diet. Food intake, body weight, and adiposity during the 7-wk test period were relatively stable in the vehicle-treated rats (n = 16). None of 10 sCT dosing regimens administered in succession to a second group of rats (n = 18) produced a sustained 25-35% reduction in daily food intake for >5 days, although body weight and adiposity were reduced by 9% (587 +/- 12 vs. 651 +/- 14 g) and 22% (20.6 +/- 1.2 vs. 26.5 +/- 1.1%), respectively, across the 7-wk period. The declining inhibitory effect of sCT on daily food intake with the 6-h interinfusion interval appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of sCT on daily food intake with the 2- to 3-h interinfusion interval suggested possible receptor downregulation and tolerance to frequent sCT administration; however, food intake increased dramatically when sCT was discontinued for 1 day after apparent loss of treatment efficacy. Together, these results demonstrate the activation of a potent homeostatic response to increase food intake when sCT reduces food intake and energy reserves in diet-induced obese rats.     

Peripheral and Central Administration of Xenin and Neurotensin Suppress Food Intake in Rodents

Xenin is a 25‐amino acid peptide highly homologous to neurotensin. Xenin and neurotensin are reported to have similar biological effects. Both reduce food intake when administered centrally to fasted rats. We aimed to clarify and compare the effects of these peptides on food intake and behavior. We confirm that intracerebroventricular (ICV) administration of xenin or neurotensin reduces food intake in fasted rats, and demonstrate that both reduce food intake in satiated rats during the dark phase. Xenin reduced food intake more potently than neurotensin following ICV administration. ICV injection of either peptide in the dark phase increased resting behavior. Xenin and neurotensin stimulated the release of corticotrophin‐releasing hormone (CRH) from ex vivo hypothalamic explants, and administration of α‐helical CRH attenuated their effects on food intake. Intraperitoneal (IP) administration of xenin or neurotensin acutely reduced food intake in fasted mice and ad libitum fed mice in the dark phase. However, chronic continuous or twice daily peripheral administration of xenin or neurotensin to mice had no significant effect on daily food intake or body weight. These studies confirm that ICV xenin or neurotensin can acutely reduce food intake and demonstrate that peripheral administration of xenin and neurotensin also reduces food intake. This may be partly mediated by changes in hypothalamic CRH release. The lack of chronic effects on body weight observed in our experiments suggests that xenin and neurotensin are unlikely to be useful as obesity therapies.     

Serum leptin, lipids, free fatty acids, and fat pads in long-term dehydroepiandrosterone-treated Zucker rats

The obese Zucker rat has a genetically flawed leptin system and is a model of hyperphagia, obesity, hyperlipidemia, and markedly elevated leptin levels. Dehydroepiandrosterone (DHEA) administration reduces hyperphagia, hyperlipidemia, and obesity in Zucker rats. Since serum leptin levels are associated with body fat, we wondered what the effects of fat pad weight reduction from DHEA administration would have on leptin levels. This experiment investigated the effects of DHEA on intra-abdominal fat pads, serum lipids, and peripheral leptin in male lean and obese Zucker rats that were administered DHEA in their food from 4 weeks of age to 20 weeks. Lean and obese rats received plain chow or chow containing DHEA. Additional chow-fed groups of lean and obese weight-matched controls and obese pair-fed rats helped to control for the reduced body weight, food intake, and fat pad weights seen with DHEA administration. DHEA administration to lean Zucker rats reduced body weight and fat pad weights, but leptin levels showed a lower trend. Among obese rats, both DHEA treatment and pair-feeding reduced body weight and fat pad weights, but only DHEA lowered leptin levels. The weight-matched controls had reductions in fat pad weights similar to the DHEA-treated group, but with increased leptin levels. Thus, DHEA may exert a small, independent effect on leptin levels in this animal model, but the reduction is less than what would be expected.     

Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats

Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky (fa(k)/fa(k)) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs.     

Ghrelin-Induced Orexigenic Effect in Rats Depends on the Metabolic Status and Is Counteracted by Peripheral CB1 Receptor Antagonism

Ghrelin is an endogenous regulator of energy homeostasis synthesized by the stomach to stimulate appetite and positive energy balance. Similarly, the endocannabinoid system is part of our internal machinery controlling food intake and energy expenditure. Both peripheral and central mechanisms regulate CB1-mediated control of food intake and a functional relationship between hypothalamic ghrelin and cannabinoid CB1 receptor has been proposed. First of all, we investigated brain ghrelin actions on food intake in rats with different metabolic status (negative or equilibrate energy balance). Secondly, we tested a sub-anxiogenic ultra-low dose of the CB1 antagonist SR141716A (Rimonabant) and the peripheral-acting CB1 antagonist LH-21 on ghrelin orexigenic actions. We found that: 1) central administration of ghrelin promotes food intake in free feeding animals but not in 24 h food-deprived or chronically food-restricted animals; 2) an ultra-low dose of SR141716A (a subthreshold dose 75 folds lower than the EC₅₀ for induction of anxiety) completely counteracts the orexigenic actions of central ghrelin in free feeding animals; 3) the peripheral-restricted CB1 antagonist LH-21 blocks ghrelin-induced hyperphagia in free feeding animals. Our study highlights the importance of the animaĺs metabolic status for the effectiveness of ghrelin in promoting feeding, and suggests that the peripheral endocannabinoid system may interact with ghrelińs signal in the control of food intake under equilibrate energy balance conditions.     

Effects of different intermittent peptide YY (3-36) dosing strategies on food intake, body weight, and adiposity in diet-induced obese rats

Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces either no effect or a transient reduction in food intake and body weight. Our aim here was to identify an intermittent dosing strategy for intraperitoneal infusion of peptide YY(3-36) [PYY(3-36)] that produces a sustained reduction in daily food intake and adiposity in diet-induced obese rats. Rats (665+/-10 g body wt, 166+/-7 g body fat) with intraperitoneal catheters tethered to infusion swivels had free access to a high-fat diet. Vehicle-treated rats (n=23) had relatively stable food intake, body weight, and adiposity during the 9-wk test period. None of 15 PYY(3-36) dosing regimens administered in succession to a second group of rats (n=22) produced a sustained 15-25% reduction in daily food intake for >5 days, although body weight and adiposity were reduced across the 9-wk period by 12% (594+/-15 vs. 672+/-15 g) and 43% (96+/-7 vs. 169+/-9 g), respectively. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was >or=3 h appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was <3 h suggested possible receptor downregulation and tolerance to frequent PYY(3-36) administration; however, food intake significantly increased when PYY(3-36) treatments were discontinued for 1 day following apparent loss in treatment efficacies. Together, these results demonstrate the development of a potent homeostatic response to increase food intake when PYY(3-36) reduces food intake and energy reserves in diet-induced obese rats.     

Differential effect of polyherbal,antiobesity preparation,OB-200G in male and female mice and monosodium glutamate-treated rats

Effect of administration of different doses (0.25, 0.5, 1 and 2 g/kg, twice daily, po) of a polyherbal preparation, OB-200G and fluoxetine (10 mg/kg, ip) for 21 days was studied on food intake and body weight in male and female Laka mice. The study further investigated the effect of administration of 0.5 g/kg dose of OB-200G for 40 days on body weight, fat pad weights, locomotor activity and biochemical parameters in monosodium glutamate (MSG)-treated male and female Wistar rat pups. Administration of OB-200G produced dose dependent decrease in body weight in both male and female mice. On the other hand, fluoxetine decreased body weight only in female mice. The food intake was significantly (P < 0.05) increased in both fasted male and female mice after treatment with the lower dose (0.25 g/kg, po) of OB-200G. However, significant (P < 0.05) decrease in food intake was recorded with the administration of higher doses (0.5, 1 and 2 g/kg, po) of OB-200G and fluoxetine in fasted female mice on day 1, 7, 14 and 21. But in male mice differential effect on food intake was recorded at different doses on day 1, 7, 14 and 21. Further, OB-200G administration significantly (P < 0.05) decreased body weight and fat pad weights, increased serum glucose levels and ambulatory activity in MSG-treated female rats but not in MSG-treated male rats. The results suggest that OB-200G involves gender differences in mediating its antiobesity effect and may supplement the current armamentarium for the treatment of obesity.     

Involvement of stomach ghrelin and hypothalamic neuropeptides in tumor necrosis factor-alpha-induced hypophagia in mice

This study aimed to clarify the interaction of tumor necrosis factor-alpha (TNF-alpha), an anorexigenic cytokine, with ghrelin, an orexigenic peptide secreted by the stomach lining, and hypothalamic neuropeptides in the regulation of food intake in mice. The peripheral administration of TNF-alpha dose-dependently decreased the 24-h cumulative food intake compared with the administration of saline. Reduced food intake was observed at 6 h and 24 h. The same TNF-alpha treatment significantly decreased the plasma level of ghrelin at 6 h and 24 h after treatment compared with the control levels. These changes were accompanied by a significant reduction in the expression of ghrelin mRNA in the stomach at 24 h after treatment. TNF-alpha treatment also resulted in a significant increase in expression of pro-opiomelanocortin (POMC) mRNA and a significant decrease in expression of agouti-related protein (AGRP) mRNA in the hypothalamus at 6 h after treatment. Finally, the pre-administration of ghrelin, reversed the TNF-alpha-induced hypophagia in mice at 6 and 24 h. Taken together, these findings suggest that hypothalamic POMC and AGRP and stomach ghrelin may be involved in TNF-alpha-induced hypophagia in mice.     

The influence of long-term melatonin administration on basic physiological and metabolic variables of young Wistar:Han rats

The question of effects of long-term melatonin (MEL) administration have not yet been explained sufficiently, especially its metabolic consequences in young persons and animals. The aim of the present study was to analyze the effects of MEL given during prolonged time (for 3 months) and chronically (for 6 months) at the dose of 4 μg/mL of tap water, on the selected metabolic and hormonal parameters in young female and male Wistar:Han (WH) rats. The weights of selected organs, tissues, body weight gains and food and water intake were registered. Six weeks aged rats were adapted to standard housing conditions and light regimen L:D=12:12 h, fed standard laboratory diet and drank tap water (controls) or MEL solution ad libitum; finally they were sacrificed after overnight fasting. Prolonged MEL administration decreased serum glucose concentration and increased triacylglycerol and malondialdehyde concentration/content in the liver in females. In males MEL increased concentrations of serum phospholipids, corticosterone and liver malondialdehyde. MEL treatment reduced the body weight in both sexes and weight of epididymal fat in males, without any alterations of food and water intake. Chronic MEL administration reduced serum glucose concentration and increased concentration/content of glycogen, triacylglycerol and cholesterol in the liver and glycogen concentration/content in heart muscle in males. In females, the significant rise of serum corticosterone concentration and liver malondialdehyde content was recorded. MEL significantly increased liver weight and decreased thymus weight in males. MEL administration increased temporarily water intake in males, body and epididymal fat weights were similar to that in controls. Body weight of MEL drinking females was reduced in the 1^st half of experiment only; the food and water intake did not differ from control group. The response in WH rats on MEL was more prominent as in the Sprague-Dawley strain (our previous studies). Male rats were generally more affected, probably due to higher daily and total consumption of melatonin.     

Dietary soy isoflavone-aglycone lowers food intake in female rats with and without ovariectomy

Objective: Estrogens downregulate eating behavior, and soy isoflavones are known to be estrogenic agents. We aimed to examine whether the estrogenic property of soy isoflavones can affect food intake and body weight. Methods and Procedures: Seven‐week‐old male, female, and ovariectomized (OVX) Sprague‐Dawley rats were given free access to a diet containing 100–300 mg total isoflavone/kg diet, or to a control diet, either with or without concurrent administration of estradiol by subcutaneous implantation. Results: Dietary soy isoflavone was shown to lower food intake in female rats, whether or not the animals had undergone ovariectomy. Administration of estradiol lowered the food intake in male rats and in OVX female rats. The decrease in weekly food intake in female rats led to a reduction in their weekly gain in body weight. Dietary soy isoflavone significantly increased the concentration of serum isoflavones, especially equol (a metabolite of daidzein), regardless of gender or ovariectomy. Dietary soy isoflavone did not affect either serum estradiol concentration or uterine and didymus weights, but estradiol administration improved the uterine atrophy in OVX rats, and decreased the didymus weight in male rats. Discussion: Soy isoflavone lowers the food intake in female rats, but not in the male animals. Contrary to the hypothesis currently in vogue, the reduction in food intake caused by soy isoflavone may not be a purely estrogenic effect. This follows from the finding that the effects of soy isoflavones on food intake and on the reproductive organs differ from the corresponding effects produced by estrogen.     

Does neuropeptide Y contribute to the anorectic action of amylin?

Neuropeptide Y (NPY) is a potent feeding stimulant acting at the level of the hypothalamus. Amylin, a peptide co-released with insulin from pancreatic beta cells, inhibits feeding following peripheral or central administration. However, the mechanism by which amylin exerts its anorectic effect is controversial. This study investigated the acute effect of amylin on food intake induced by NPY, and the effect of chronic amylin administration on food intake and body weight in male Sprague Dawley rats previously implanted with intracerebroventricular (icv) cannulae. Rats received 1 nmol NPY, followed by amylin (0.05, 0.1, 0.5 nmol) or 2 microl saline. Increasing doses of amylin resulted in a dose-dependent inhibition of NPY-induced feeding by 31%, 74% and 99%, respectively (P < 0.05). To determine the chronic effects of i.c.v. amylin administration on feeding, rats received 0.5 nmol amylin or saline daily, 30 min before dark phase, over 6 days. Amylin significantly reduced food intake at 1, 4, 16 and 24 hours; after 6 days, amylin-treated rats showed a significant reduction in body weight, having lost 17.3 +/- 6.1 g, while control animals gained 7.7 +/- 5.1 g (P < 0.05). Brain NPY concentrations were not elevated, despite the reduced food intake, suggesting amylin may regulate NPY production or release. Thus, amylin potently inhibits NPY-induced feeding and attenuates normal 24 hour food intake, leading to weight loss.