Modulation of appetite by gonadal steroid hormones

Several sex differences in eating, their control by gonadal steroid hormones and their peripheral and central mediating mechanisms are reviewed. Adult female rats and mice as well as women eat less during the peri-ovulatory phase of the ovarian cycle (estrus in rats and mice) than other phases, an effect under the control of cyclic changes in estradiol secretion. Women also appear to eat more sweets during the luteal phase of the cycle than other phases, possibly due to simultaneous increases in estradiol and progesterone. In rats and mice, gonadectomy reveals further sex differences: orchiectomy decreases food intake by decreasing meal frequency and ovariectomy increases food intake by increasing meal size. These changes are reversed by testosterone and estradiol treatment, respectively. A variety of peripheral feedback controls of eating, including ghrelin, cholecystokinin (CCK), glucagon, hepatic fatty acid oxidation, insulin and leptin, has been shown to be estradiol-sensitive under at least some conditions and may mediate the estrogenic inhibition of eating. Of these, most progress has been made in the case of CCK. Neurons expressing estrogen receptor-alpha in the nucleus tractus solitarius of the brainstem appear to increase their sensitivity to CCK-induced vagal afferent input so as to lead to an increase in the satiating potency of CCK, and consequently decreased food intake, during the peri-ovulatory period in rats. Central serotonergic mechanisms also appear to be part of the effect of estradiol on eating. The physiological roles of other peripheral feedback controls of eating and their central mediators remain to be established.     

A model of emotional stress‐induced binge eating in female mice with no history of food restriction

Overeating is a major contributing factor to obesity and related health complications. For women, in particular, negative emotions such as stress strongly influence eating behavior and bingeing episodes. Modeling this type of binge eating in rodents presents challenges: firstly, stress‐induced anorexia is commonly observed in rodents therefore a mild stressor is required in order to observe an orexigenic effect. Second, many studies report using calorie restriction to observe the required behavior; yet this does not necessarily reflect the human condition. Thus, the aim of this study was to develop a model of emotional stress‐induced bingeing independent of caloric restriction. Female and male C57BL/6J mice were divided into ad libitum (n = 20 per sex) and food‐restricted (n = 20 per sex) groups which were both further split into a control group and a group exposed to frustration stress (n = 10 per group). All mice were provided intermittent access to a highly palatable food in 2 cycles. At the end of each cycle the stress group was subjected to a 15‐minute frustration episode where highly palatable food was within the home cage but inaccessible. Both groups were then given free access for 15 minutes. Frustrated female mice from the ad libitum displayed binge‐like behavior compared with controls (P = .0001). Notably, this behavior was absent in males. Ovariectomy had no impact on binge‐like behavior. Collectively, these data validate a novel model of emotional stress‐induced binge eating specific to female mice which does not require caloric restriction and is not driven by ovarian hormones.     

The Influence of Early Life Interventions on Olfactory Memory Related to Palatable Food, and on Oxidative Stress Parameters and Na+/K+-ATPase Activity in the Hippocampus and Olfactory Bulb of Female Adult Rats

The effects of neonatal handling and the absence of ovarian hormones on the olfactory memory related to a palatable food in adulthood were investigated. Oxidative stress parameters and Na+/K+-ATPase activity in the hippocampus and olfactory bulb of adult pre-puberty ovariectomized female rats handled or not in the neonatal period were also evaluated. Litters were non-handled or handled (10 min/day, days 1-10 after birth). Females from each litter were divided into: OVX (subjected to ovariectomy), sham, and intact. When adults, olfactory memory related to a palatable food (chocolate) was evaluate using the hole-board olfactory task. Additionally, oxidative stress parameters and Na+/K+-ATPase activity were measured in the hippocampus and olfactory bulb. No difference between groups was observed considering olfactory memory evaluation. Neonatal handled rats presented an increase in Na+/K+-ATPase activity in the hippocampus and in the olfactory bulb, compared to non-handled ones. Considering the surgical procedure, there was a decrease in Na+/K+-ATPase and catalase activities in sham and OVX groups, compared to intact animals in the olfactory bulb. We concluded that olfactory memory related to a palatable food in adulthood was not affected by neonatal handling or by pre-puberty surgery, with or without removal of ovaries. The difference observed between groups in catalase and Na+/K+-ATPase activity does not seem to be related to the olfactory memory. Additionally, the increase in Na+/K+-ATPase activity (an enzyme that maintains the neurochemical gradient necessary for neuronal excitability) induced by neonatal handling may be related to neuroplastic changes in the hippocampus and olfactory bulb.     

Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves control of eating in obese subjects: a 6-wk translational research study

Evidence from rodent studies indicates that the beta-cell-derived neurohormone amylin exerts multiple effects on eating behavior, including reductions in meal size, intake of highly palatable foods, and stress-induced sucrose consumption. To assess the effect of amylin agonism on human eating behavior we conducted a randomized, blinded, placebo-controlled, multicenter study investigating the effects of the amylin analog pramlintide on body weight, 24-h caloric intake, portion sizes, "fast food" intake, and perceived control of eating in 88 obese subjects. After a 2-day placebo lead-in, subjects self-administered pramlintide (180 microg) or placebo by subcutaneous injection 15 min before meals for 6 wk without concomitant lifestyle modifications. Compared with placebo, pramlintide treatment elicited significant mean reductions from baseline in body weight on day 44 (-2.1 +/- 0.3 vs. +0.1 +/- 0.4%, P < 0.001), 24-h caloric intake (-990 +/- 94 vs. -243 +/- 126 kcal on day 3, P < 0.0001; -680 +/- 86 vs. -191 +/- 161 kcal on day 43, P < 0.01), portion sizes, and caloric intake at a "fast food challenge" (-385 +/- 61 vs. -109 +/- 88 kcal on day 44, P < 0.05). Pramlintide treatment also improved perceived control of eating, as demonstrated by a 45% placebo-corrected reduction in binge eating scores (P < 0.01). The results of this translational research study confirm in humans various preclinical effects of amylin agonism, demonstrating that pramlintide-mediated weight loss in obese subjects is accompanied by sustained reductions in 24-h food intake, portion sizes, fast food intake, and binge eating tendencies.     

Memantine reduces consumption of highly palatable food in a rat model of binge eating

Excessive consumption of highly palatable food has been linked to the development of eating disorders and obesity, and can be modeled in non-food-deprived rats by offering them a limited (2-h daily) access to an optional dietary fat. Since the glutamatergic system has recently emerged as a viable target for binge-eating medication development, we compared the effects of subchronic treatment with glutamatergic receptor antagonists to the effects of a reference appetite-suppressing agent sibutramine on highly palatable food (lard) and normal chow intake. In three separate experiments, the consumption of a standard laboratory chow and lard were measured during 12 days of medication treatment and for 6 days afterwards. Generalized estimating equations analysis demonstrated that sibutramine (7.5 mg/kg, PO) significantly decreased lard consumption, with a concurrent increase in chow consumption. Sibutramine effects disappeared after treatment discontinuation. The NMDA receptor antagonist memantine (5 mg/kg, IP) significantly decreased lard consumption and increased chow consumption, comparable to effects of sibutramine; however, memantine’s effects persisted after treatment discontinuation. The effects of the mGluR5 antagonist MTEP (7.5 mg/kg, IP) on food consumption were in the same direction as seen with memantine, but the observed differences were not significant. In an additional control experiment, sibutramine and memantine reduced unlimited (24 h) chow intake during the treatment phase. Present results provide evidence that glutamatergic neurotransmission might be involved in the regulation of excessive consumption of highly palatable foods, and suggest that NMDA receptor may be an attractive target for developing obesity and disordered eating pharmacotherapies.     

Comparison of crowding and food restriction effects on growth, body weight gain and endocrine status in the rat

The present work compares the effects of post-weaning crowding and those of food restriction on growth, body weight gain and the levels of several hormones, in male Sprague-Dawley rats. Crowding resulted in reduced food intake and diminished body weight gain. Rats daily receiving the same amount of food as that eaten by crowded rats (food-restricted group) showed similar body weight gain as crowded rats, but higher growth rate. Neither crowding nor food restriction altered the pituitary-adrenal axis. In contrast, both treatments decreased serum insulin, growth hormone (GH), somatomedin C (Sm-C) and thyroid-stimulating hormone (TSH) as compared to control rats. The reduction of GH and Sm-C levels was similar in crowded and food-restricted rats but that of TSH was higher in food-restricted, rather than in crowded rats. The present data indicate that the effects of crowding could only be partially explained by the concomittant reduction of food intake and that the serum levels of the hormones studied could not explain the differences between the crowded and food-restricted rats with regard to growth.     

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.     

Naloxone reduction of stress-related feeding

The effects of the narcotic antagonist, naloxone, on various types of stress- related feeding in rats were examined. Tail pinch-induced eating of a palatable substance, and 3 hr daytime rat chow intake following acute 2-deoxy-D-glucose (2-DG, 400 mg/kg) administration or 24 hr food deprivation were significantly decreased by low doses (1 mg/kg) of naloxone. Night time food intake was likewise decreased by naloxone (4 mg/kg). In contrast, hyperphagia induced by insulin (10 U/kg) was not decreased by naloxone (0.06–16 mg/kg). These findings suggest that narcotic antagonists should be considered as possible anorexics selective for stress-induced eating, and that endogenous opiates may prove to be another significant factor involved in the control of food intake.     

Calorie restriction prevents the development of insulin resistance and impaired insulin signaling in skeletal muscle of ovariectomized rats

Insulin resistance of skeletal muscle glucose transport due to prolonged loss of ovarian function in ovariectomized (OVX) rats is accompanied by other features of the metabolic syndrome and may be confounded by increased calorie consumption. In this study, we investigated the role of calorie consumption in the development of insulin resistance in OVX rats. In addition, we examined the cellular mechanisms underlying skeletal muscle insulin resistance in OVX rats. Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated (SHAM). OVX rats either had free access to food, pair feeding (PF) with SHAM or received a 35% reduction in food intake (calorie restriction; CR) for 12weeks. Compared with SHAM, ovariectomy induced skeletal muscle insulin resistance, which was associated with decreases (32-70%) in tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), IRS-1 associated p85 subunit of phosphatidylinositol 3-kinase (PI3-kinase), and Akt Ser(473) phosphorylation whereas insulin-stimulated phosphorylation of IRS-1 Ser(307), SAPK/JNK Thr(183)/Tyr(185), and p38 mitogen-activated protein kinase (MAPK) Thr(180)/Tyr(182) was increased (24-62%). PF improved the serum lipid profile but did not restore insulin-stimulated glucose transport, indicating that insulin resistance in OVX rats is a consequence of ovarian hormone deprivation. In contrast, impaired insulin sensitivity and defective insulin signaling were not observed in the skeletal muscle of OVX+CR rats. Therefore, we provide evidence for the first time that CR effectively prevents the development of insulin resistance and impaired insulin signaling in the skeletal muscle of OVX rats.     

Morphological and functional study of the GH-immunoreactive adenohypophyseal cells in ovariectomized rats

Summary In view of the existence of a different secretion pattern of growth hormone (GH) between male and female rats, the aim of the present study was to analyse the role played by ovarian steroid hormones in the modulation of such secretion. To do so, postpuberal female rats were ovariectomized and killed at 30 days after the operation. The basal serum levels of growth hormone, together with cell area, cytoplasmic area and nuclear area of the hypophyseal somatotropic cells of normal and ovariectomized rats were compared. The results obtained show that ovariectomy induces a significant decrease (p<0.05) in the basal serum levels of GH, accompanied by an increase in cellular and cytoplasmic areas, with no significant differences in nuclear area. Overiectomy was also accompanied by an increase in reaction intensity and the number of GH-immunoreactive cells (p<0.01). These findings point to the shift towards a masculine secretory and morphological pattern following ovariectomy and supports the hypothesis that ovarian steroids intervene in the establishment of a different pattern in females compared to males.     

Classification of feeding and eating disorders: review of evidence and proposals for ICD-11

Current classification of eating disorders is failing to classify most clinical presentations; ignores continuities between child, adolescent and adult manifestations; and requires frequent changes of diagnosis to accommodate the natural course of these disorders. The classification is divorced from clinical practice, and investigators of clinical trials have felt compelled to introduce unsystematic modifications. Classification of feeding and eating disorders in ICD-11 requires substantial changes to remediate the shortcomings. We review evidence on the developmental and cross-cultural differences and continuities, course and distinctive features of feeding and eating disorders. We make the following recommendations: a) feeding and eating disorders should be merged into a single grouping with categories applicable across age groups; b) the category of anorexia nervosa should be broadened through dropping the requirement for amenorrhoea, extending the weight criterion to any significant underweight, and extending the cognitive criterion to include developmentally and culturally relevant presentations; c) a severity qualifier "with dangerously low body weight" should distinguish the severe cases of anorexia nervosa that carry the riskiest prognosis; d) bulimia nervosa should be extended to include subjective binge eating; e) binge eating disorder should be included as a specific category defined by subjective or objective binge eating in the absence of regular compensatory behaviour; f) combined eating disorder should classify subjects who sequentially or concurrently fulfil criteria for both anorexia and bulimia nervosa; g) avoidant/restrictive food intake disorder should classify restricted food intake in children or adults that is not accompanied by body weight and shape related psychopathology; h) a uniform minimum duration criterion of four weeks should apply.     

Regulation of Resistin by Gonadal,Thyroid Hormone,and Nutritional Status

Objective: Resistin was recently identified as a hormone secreted by adipocytes that is under hormonal and nutritional control. This hormone has been suggested to be the link between obesity and type 2 diabetes. The aim of this study was to assess the influence of gender, gonadal status, thyroid hormones, pregnancy, and food restriction on resistin mRNA levels in adipose tissue of rats. Research Methods and Procedures: We have determined resistin mRNA expression by Northern blot analysis in all experimental sets. Results: Resistin mRNA expression is influenced by age, with the highest hormone levels existing at 45 days after birth and decreasing thereafter. Resistin mRNA expression is higher in men than in women. Moreover, we studied the effect of orchidectomy and ovariectomy in rats of different ages and showed that gonadal hormones increase adipose tissue resistin mRNA expression in male rats. Resistin is also regulated by thyroid hormones; it is severely decreased in hyperthyroid rats. Our results clearly show that chronic food restriction (30% of ad libitum food intake) led to a decrease in adipose tissue mRNA levels in normal cycling female rats and pregnant rats. In pregnancy, resistin mRNA levels were enhanced particularly at midgestation. Discussion: Our observations indicate that resistin is influenced by gender, gonadal status, thyroid hormones, and pregnancy. These findings suggest that resistin could explain the decreased insulin sensitivity during puberty and could be the link between sex steroids and insulin sensitivity. Moreover, resistin could mediate the effect of thyroid hormones on insulin resistance and the state of insulin resistance present during pregnancy.     

Inhibiting food reward: delay discounting, food reward sensitivity, and palatable food intake in overweight and obese women

Overeating is believed to result when the appetitive motivation to consume palatable food exceeds an individual's capacity for inhibitory control of eating. This hypothesis was supported in recent studies involving predominantly normal weight women, but has not been tested in obese populations. The current study tested the interaction between food reward sensitivity and inhibitory control in predicting palatable food intake among energy-replete overweight and obese women (N = 62). Sensitivity to palatable food reward was measured with the Power of Food Scale. Inhibitory control was assessed with a computerized choice task that captures the tendency to discount large delayed rewards relative to smaller immediate rewards. Participants completed an eating in the absence of hunger protocol in which homeostatic energy needs were eliminated with a bland preload of plain oatmeal, followed by a bogus laboratory taste test of palatable and bland snacks. The interaction between food reward sensitivity and inhibitory control was a significant predictor of palatable food intake in regression analyses controlling for BMI and the amount of preload consumed. Probing this interaction indicated that higher food reward sensitivity predicted greater palatable food intake at low levels of inhibitory control, but was not associated with intake at high levels of inhibitory control. As expected, no associations were found in a similar regression analysis predicting intake of bland foods. Findings support a neurobehavioral model of eating behavior in which sensitivity to palatable food reward drives overeating only when accompanied by insufficient inhibitory control. Strengthening inhibitory control could enhance weight management programs.     

A Model of Binge‐Like Eating Behavior in Mice That Does Not Require Food Deprivation or Stress

Binge eating disorder (BED) is characterized by excessive food intake during a short period of time and is often associated with obesity. Mouse models of binge‐like eating behavior are lacking making it difficult to employ genetic models in the identification of mechanisms regulating excessive eating. We report a rapid and simple model to induce binge‐like eating behavior in mice that does not require food deprivation or exogenous stressors. Weekly 24 h access to a nutritionally complete high energy diet (HED), along with continuous access to standard chow, resulted in a significant increase in HED intake following its presentation compared to mice that had continuous access to both diets. Mice exhibiting binge‐like eating consumed one‐third of their normal total daily caloric intake within 2.5 h of HED presentation. Moreover, total 24‐h caloric intakes were increased by 50% in mice exhibiting binge‐like eating. Following repeated cycles, binge‐like eating of the HED was maintained over several weeks with no evidence of habituation or significant alterations in body weight and adiposity. Pharmacological evaluation of binge‐like eating behavior was performed using clinically employed compounds. Interestingly, binge‐like eating was dose‐dependently decreased by fluoxetine, but not baclofen or topiramate. These data support clinical validation of this mouse model of binge‐like eating behavior, as fluoxetine has been shown to reduce binge frequency in human subjects with BED. The availability of transgenic and knockout mice will allow for the determination of genes that are involved in the initiation and maintenance of binge‐like eating behavior.     

Glucagon-like peptide-1 (GLP-1) increases in plasma and colon tissue prior to estrus and circulating levels change with increasing age in reproductively competent Wistar rats

There is a well-documented association between cyclic changes to food intake and the changing ovarian hormone levels of the reproductive cycle in female mammals. Limited research on appetite-controlling gastrointestinal peptides has taken place in females, simply because regular reproductive changes in steroid hormones present additional experimental factors to account for. This study focussed directly on the roles that gastrointestinal-secreted peptides may have in these reported, naturally occurring, changes to food intake during the rodent estrous cycle and aimed to determine whether peripheral changes occurred in the anorexigenic (appetite-reducing) hormones peptide-YY (PYY) and glucagon-like peptide-1 (GLP-1) in female Wistar rats (32–44 weeks of age). Total forms of each peptide were measured in matched fed and fasted plasma and descending colon tissue samples for each animal during the dark (feeding) phase. PYY concentrations did not significantly change between defined cycle stages, in either plasma or tissue samples. GLP-1 concentrations in fed plasma and descending colon tissue were significantly increased during proestrus, just prior to a significant reduction in fasted stomach contents at estrus, suggesting increased satiety and reduced food intake at this stage of the cycle. Increased proestrus GLP-1 concentrations could contribute to the reported reduction in food intake during estrus and may also have biological importance in providing the optimal nutritional and metabolic environment for gametes at the potential point of conception. Additional analysis of the findings demonstrated significant interactions of ovarian cycle stage and fed/fasted status with age on GLP-1, but not PYY plasma concentrations. Slightly older females had reduced fed plasma GLP-1 suggesting that a relaxation of regulatory control of this incretin hormone may also take place with increasing age in reproductively competent females.     

Bingeing,Self‐restriction,and Increased Body Weight in Rats With Limited Access to a Sweet‐fat Diet

Objective: Prior research has shown that fasting alternated with a diet of standard rodent chow and a 10% sucrose solution produces bingeing on the sucrose, but animals remain at normal body weight. The present study investigated whether restricted access to a highly palatable combination of sugar and fat, without food deprivation, would instigate binge eating and also increase body weight. Methods and Procedures: Male rats were maintained for 25 days on one of four diets: (i) sweet‐fat chow for 2 h/day followed by ad libitum standard chow, (ii) 2‐h sweet‐fat chow only 3 days/week and access to standard chow the rest of the time, (iii) ad libitum sweet‐fat chow, or (iv) ad libitum standard chow. Results: Both groups with 2‐h access to the sweet‐fat chow exhibited bingeing behavior, as defined by excessively large meals. The body weight of these animals increased due to large meals and then decreased between binges as a result of self‐restricted intake of standard chow following binges. However, despite these fluctuations in body weight, the group with 2‐h access to sweet‐fat chow every day gained significantly more weight than the control group with standard chow available ad libitum. Discussion: These findings may have implications for the body weight fluctuations associated with binge‐eating disorder, as well as the relationship between binge eating and the obesity epidemic.     

Time Trends in Population Prevalence of Eating Disorder Behaviors and Their Relationship to Quality of Life

Objective

To examine temporal trends in the burden of eating disorder (ED) features, as estimated by the composite of their prevalence and impact upon quality of life (QoL) over a period of 10 years.

Methodology

Representative samples of 3010 participants in 1998 and 3034 participants in 2008 from the South Australian adult population were assessed for endorsement of ED features (objective binge eating, extreme dieting, and purging were assessed in both years; subjective binge eating and extreme weight/shape concerns were also assessed in 2008) and QoL using the Medical Outcomes Study Short Form (SF-36).

Principal Findings

From 1998 to 2008 significant increases in the prevalence of objective binge eating (2.7% to 4.9%, p<0.01) and extreme dieting (1.5% to 3.3%, p<0.01), but not purging, were observed. Lower scores on the SF-36 were significantly associated with endorsement of any of these behaviors in both 1998 and 2008 (all p<0.001). No significant difference was observed in the effect of the endorsement of these ED behaviors on QoL between 1998 and 2008 (all p>0.05). Multiple linear regressions found that in 1998 only objective binge eating significantly predicted scores on the mental health summary scale of the SF-36; however, in 2008 extreme weight/shape concerns, extreme dieting, and subjective binge eating were also significant predictors. Objective binge eating and extreme dieting were significant predictors of scores on the physical health summary scale of the SF-36 in both 1998 and 2008.

Conclusions and Significance

The prevalence of ED behaviors increased between 1998 and 2008, while their impact on QoL remained stable. This suggests an overall increase in the burden of disordered eating from 1998 to 2008. Given that binge eating and extreme dieting predict impairment in QoL, the necessity of interventions to prevent both under- and over-eating is reinforced.     

Diltiazem enhances food intake and gastrointestinal function in rats

The present study was to investigate the effects of diltiazem, a ghrelin receptor agonist, on food intake and gastrointestinal functions in rats. Rats were intragastrically administered with diltiazem solution (daily 16 mg/kg, 30 mg/kg or 80 mg/kg, 30 d), and the rats with saline as control. To detect the effects of diltiazem on food intake and body weight, the average daily food intake and body weight were recorded, and the serum metabolic hormones of plasma growth hormone (GH) and neuropeptide Y (NPY) were tested by radioimmunoassay. By means of the spectrophotometer and the modified Mett's method, the effects of diltiazem on rat's gastrointestinal function and pepsin activity were tested, respectively. In addition, the gastric juice's acidity of rats was detected by titration and the secretion amount was calculated. The results showed that the food intake and body weight were maximally promoted by diltiazem at the dose of 30 mg/kg daily (30 d). The average daily food intake and body weight were significantly increased, and the serum concentrations of GH and NPY were also remarkably increased in diltiazem-treated groups compared with those in control group. The results also showed that the gastric emptying rate, gastric acid secretion and the activity of pepsin were significantly increased in diltiazem-treated group compared with those in control group. These results suggest that diltiazem induces enhancement of eating, in the same time, it can also stimulate the gastrointestinal function and regulate growth of rat.     

Centrally Administered Ghrelin Acutely Influences Food Choice in Rodents

We sought to determine whether the orexigenic hormone, ghrelin, is involved in the intrinsic regulation of food choice in rats. Ghrelin would seem suited to serve such a role given that it signals hunger information from the stomach to brain areas important for feeding control, including the hypothalamus and reward system (e.g. ventral tegmental area, VTA). Thus, in rats offered a choice of palatable foods (sucrose pellets and lard) superimposed on regular chow for 2 weeks, we explored whether acute central delivery of ghrelin (intracerebroventricular (ICV) or intra-VTA) is able to redirect their dietary choice. The major unexpected finding is that, in rats with high baseline lard intake, acute ICV ghrelin injection increased their chow intake over 3-fold, relative to vehicle-injected controls, measured at both 3 hr and 6 hr after injection. Similar effects were observed when ghrelin was delivered to the VTA, thereby identifying the VTA as a likely contributing neurobiological substrate for these effects. We also explored food choice after an overnight fast, when endogenous ghrelin levels are elevated, and found similar effects of dietary choice to those described for ghrelin. These effects of fasting on food choice were suppressed in models of suppressed ghrelin signaling (i.e. peripheral injection of a ghrelin receptor antagonist to rats and ghrelin receptor (GHSR) knock-out mice), implicating a role for endogenous ghrelin in the changes in food choice that occur after an overnight fast. Thus, in line with its role as a gut-brain hunger hormone, ghrelin appears to be able to acutely alter food choice, with notable effects to promote “healthy” chow intake, and identify the VTA as a likely contributing neurobiological substrate for these effects.     

Effects of ovarian hormones on eating behaviors, body weight, and glucoregulation in rhesus monkeys

The influences of ovarian hormones on food intake, taste preferences, and glucoregulation were examined in intact and ovariectomized rhesus monkeys. Intake of intact monkeys was lowest in the preovulatory stage of the cycle, when estrogen levels are elevated, and exogenous estradiol transiently suppressed food intake of ovariectomized monkeys in a dose-related manner, confirming previous observations. Progesterone treatment did not affect food intake when given alone, but it did attenuate the effect of estradiol when both hormones were given concurrently. Preferences for sweet solutions were not detectably influenced by chronic treatment with estradiol or progesterone, and compensatory responses to ingestion of sugar were unaltered by hormone treatment. Glucose tolerance tests did not reveal significant influences of ovarian hormones on glycemia, but insulin levels were elevated during periods of progesterone treatment. These results do not support the suggestion that fluctuations in caloric intake during the menstrual cycle are secondary to changes in taste preference or glucoregulation. However, possible changes in sweet preference and glucoregulation shortly after initiation of estrogen treatment, i.e., during the time of suppressed food intake, remain to be examined.