Appetite-regulating Peptides Research Articles

Treatment of genetically obese mice with the iminosugar N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin reduces body weight by decreasing food intake and increasing fat oxidation

Obesity and its associated conditions such as type 2 diabetes mellitus are major causes of morbidity and mortality. The iminosugar N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin (AMP-DNM) improves insulin sensitivity in rodent models of insulin resistance and type 2 diabetes mellitus. In the current study, we characterized the impact of AMP-DNM on substrate oxidation patterns, food intake, and body weight gain in obese mice. Eight ob/ob mice treated with 100 mg/(kg d) AMP-DNM mixed in the food and 8 control ob/ob mice were placed in metabolic cages during the first, third, and fifth week of the experiment for measurement of substrate oxidation rates, energy expenditure, activity, and food intake. Mice were killed after 6 weeks of treatment. Initiation of treatment with AMP-DNM resulted in a rapid increase in fat oxidation by 129% ( P = .05), a decrease in carbohydrate oxidation by 35% ( P = .01), and a reduction in food intake by approximately 26% ( P < .01) compared with control mice. Treatment with AMP-DNM decreased hepatic triglyceride content by 66% ( P < .01) and, in line with the elevated fat oxidation rates, increased hepatic carnitine palmitoyl transferase 1a expression. Treatment with AMP-DNM increased plasma levels of the appetite-regulating peptide YY compared with control mice. Treatment with AMP-DNM rapidly reduces food intake and increases fat oxidation, resulting in improvement of the obese phenotype. These features of AMP-DNM, together with its insulin-sensitizing capacity, make it an attractive candidate drug for the treatment of obesity and its associated metabolic derangements.

Knockdown of NPY Expression in the Dorsomedial Hypothalamus Promotes Development of Brown Adipocytes and Prevents Diet-Induced Obesity

Hypothalamic neuropeptide Y (NPY) has been implicated in control of energy balance, but the physiological importance of NPY in the dorsomedial hypothalamus (DMH) remains unclear. Here we report that knockdown of NPY expression in the DMH by adeno-associated virus-mediated RNAi reduced fat depots in rats fed regular chow and ameliorated high-fat diet-induced hyperphagia and obesity. DMH NPY knockdown resulted in development of brown adipocytes in inguinal white adipose tissue through the sympathetic nervous system. This knockdown increased uncoupling protein 1 expression in both inguinal fat and interscapular brown adipose tissue (BAT). Consistent with the activation of BAT, DMH NPY knockdown increased energy expenditure and enhanced the thermogenic response to a cold environment. This knockdown also increased locomotor activity, improved glucose homeostasis, and enhanced insulin sensitivity. Together, these results demonstrate critical roles of DMH NPY in body weight regulation through affecting food intake, body adiposity, thermogenesis, energy expenditure, and physical activity.

Cognitive flexibility and Agouti-related protein in adolescent patients with anorexia nervosa

Cognitive flexibility and the flexible learning and relearning of stimulus-reward-associations are important for decision-making and goal-directed behavior. Studies on patients with anorexia nervosa (AN) have shown difficulties in cognitive functions associated with malnutrition and extreme underweight. However, to date we find a lack of neuropsychological studies on cognitive flexibility among adolescent patients with AN. Furthermore, the underlying biological mechanisms remain unclear. Therefore, we aim to examine cognitive functions, especially reward association learning, as a measure of cognitive flexibility in adolescent patients with AN and investigate the relationship between Agouti-related protein (AGRP) and cognitive functions. The study population consists of 30 patients with AN (M(age)=16.2 ± 1.2) and a healthy control group (CG) of 28 female adolescents (M(age)=16.3 ± 1.3). All subjects completed a neuropsychological test battery including the probabilistic Object Reversal Task, the Digit Symbol Test and the Trail Making Test. Patients with AN were explored before and after weight gain, the CG initially and after 3 months. Subtle deficits in cognitive flexibility were found in patients with AN compared to the CG. After weight gain, the AN group improved relative to their baseline values in most of the variables but did not reach CG values. They still showed slight impairments. Moreover the study revealed a clear association between AGRP levels and cognitive flexibility. Cognitive flexibility plays an important role in AN and may be modulated by abnormal levels of the appetite-regulating peptide AGRP. Even subtle impairments in cognitive flexibility can be relevant for the ability to fully engage in therapy and therefore may hinder a prosperous treatment.

The effects of morphine and nicotine co-administration on body weight, food intake and appetite-regulating peptides in rats.

Summary Previous studies in humans and animals have reported that nicotine administration decreases body weight and caloric intake. Opiate and cigarette have been used concomitantly as drug abuse. The aim of the present study was, therefore, to analyze the effect of chronic co-administration of nicotine and morphine on food intake, body weight and on some feeding-associated peptides. All experiments were carried out on male Wistar rats. Animals were randomly assigned to the free-fed and pair-fed control groups, nicotine- and morphine-treated and nicotine plus morphine groups. Morphine sulfate (20 mg/kg for 14 days s.c.) and nicotine (4 mg/kg for 14 days i.p.) were injected to the rats. The serum levels of leptin and neuropeptide Y (NPY) were measured by enzyme immunosorbant assay and radioimmunoassay, respectively. The results showed that nicotine had a greater suppressing effect on total food intake than morphine alone or nicotine plus morphine. Furthermore, chronic injection of nicotine significantly decreased body weight as compared with before injection, while body weight changes were not observed in morphine-treated rats. The mean body weight in the morphine-treated rats was lower than that in the free-fed control animals. The serum level of NPY was decreased just in the nicotine-injected group. A significant decrease in leptin levels was observed in the drug treated and pair-fed groups. In conclusion, morphine modulates the decreasing effect of nicotine on food intake, and it seems that the mechanism underlying the attenuating effects of morphine on the nicotine effects involves mediation, at least in part, by preventing the effect of nicotine on NPY levels.

Glucocorticoids decrease body weight and food intake and inhibit appetite regulatory peptide expression in the hypothalamus of rats

The aim of the present study was to investigate the effects of glucocorticoids (GCs) on appetite and gene expression of the hypothalamic appetite regulatory peptides, neuropeptide Y (NPY), agouti-related protein (AGRP) and cocaine and amphetamine-regulated transcript (CART), in non-obese and obese rats. Both non-obese and obese rats were randomly assigned to three groups: normal saline, low- and high-dose GC groups (NSG, LDG and HDG, respectively), which received an intraperitoneal injection with normal saline (0.2 ml/100 g) or hydrocortisone sodium succinate at 5 and 15 mg/kg, respectively, for 20 days. The expression levels of NPY, AGRP and CART mRNA in the hypothalamus were measured by real-time quantitative PCR. Non-obese and obese rats were found to undergo weight loss after GC injection, and a higher degree of weight loss was observed in the HDG rats. The average and cumulative food intakes in the obese and non-obese rats injected with high-dose GC were lower compared to that in the NSG (p<0.05). mRNA expression levels of the orexigenic neuropeptides, NPY and AGRP, and the anorexigenic neuropeptide, CART, were significantly lower in the HDG than levels in the NSG for both the obese and non-obese rats (p<0.05). GC treatment decreased appetite and body weight, induced apparent glucolipid metabolic disturbances and hyperinsulinemia, while down-regulated mRNA expression levels of the orexigenic neuropeptides, NPY and AGRP, and anorexigenic neuropeptide, CART, in the hypothalamus in the rats. The mechanism which induces this neuropeptide expression requires further study.

Androgen Receptor Polyglutamine Length Does Not Influence Serum Levels of Adipocytokines in Alcoholism: A Preliminary Retrospective Analysis

In recent years, various studies were able to show a link between serum levels of appetite-regulating peptides and alcoholism. The adipocytokines, adiponectin and resistin seem to be altered during withdrawal. We recently showed that a trinucleotide polymorphism within the coding region of the androgen receptor (AR) is linked to craving in alcohol withdrawal, an effect that was mostly mediated by leptin. The aim of the present preliminary retrospective study was to further elucidate whether adiponectin and resistin serum levels are regulated by this AR polymorphism as well. We included 50 male in-patients who were admitted for detoxification treatment. Each had a diagnosis of alcohol dependence (DSM-IV). Our analyses revealed that adiponectin serum levels significantly decreased, whereas resistin levels slightly increased between the day of admission and Day 7. Beyond that, we were not able to demonstrate significant associations between the investigated CAG polymorphism of the AR and adiponectin, resistin or leptin-corrected adipocytokines, either on the day of admission or on Day 7. Moreover, the polymorphism did not influence the time response of adiponectin and resistin during withdrawal. Genetic determinants of the AR influence alcohol withdrawal. Anyway, this preliminary retrospective analysis does not support the hypothesis that the investigated AR polymorphism has a major modifying effect on adiponectin or resistin serum levels in patients with alcoholism.

Control of bone remodeling by nervous system. Regulation of bone metabolism by appetite regulating neuropeptides

The traditional view of bone metabolism as a primarily endocrine activity has been expanded in recent years following the identification of nervous system controlling bone metabolism by leptin studies. Especially, hypothalamic appetite regulating-peptides, such as NPY, CART and NMU have been demonstrated to be bone-regulating neuropeptides. Recently, other neuropeptides, such as serotonin and oxytocin, are reported to be associated with bone metabolism.

Age‐associated changes of appetite‐regulating peptides

Aging is associated with a progressive decrease in appetite and food intake. The reasons for the decline in food intake are multifactorial, and relate to both peripheral and central mechanisms. Current studies about the regulation of food intake suggest that there are many central mediators that control the appetite. To determine the mechanism of age-associated decrease in appetite and food intake, we focused on the age-associated changes of the suppressing and stimulatory effect of some appetite-regulating peptides. At first, we examined cholecystokinin (CCK), one of the typical appetite-suppressing factors. Although sensitivity to CCK is enhanced in old animals, the mechanism underlying this effect has not been elucidated. Next, we focused on the appetite-stimulating peptides, orexin-A, neuropeptide Y (NPY) and ghrelin, which are known to play a critical role in food intake. To determine the age-associated decrease in appetite and food intake, we compared the stimulatory effect of intracerebroventricular administration of orexin-A, NPY and ghrelin. We report the studies of the age-associated changes of appetite-regulating peptides in this review.

Ghrelin and Obestatin Circadian Levels Differentiate Bingeing-Purging from Restrictive Anorexia Nervosa

Anorexia nervosa (AN) patients present with restrictive food behavior (AN-R). Some of them develop episodes of bulimia (AN-BP) without any clear pathophysiological explanation to date. Their clinical differentiation is important but not easily performed. Orexigenic/anorexigenic peptides measurements could provide some clues for that matter. The objective of the study was to determine whether the circadian profile of total and acylated ghrelin, obestatin, and peptide YY (PYY) levels is different in AN-R subjects when compared with AN-BP patients. This was a cross-sectional study in an endocrinological unit. Four groups of age-matched young women: 22 AN-R, 10 AN-BP, 16 normal-weight bulimia nervosa (BN), and nine controls. Twelve-point circadian profiles of plasma total and acylated ghrelin, obestatin, and PYY were measured. Total and acylated ghrelin and obestatin circadian levels were increased in AN-R when compared with controls but decreased in both AN-BP and BN groups (P < 0.001). PYY was decreased in all groups with eating disorders. Acylated to total ghrelin ratio was decreased in AN-BP and BN (P < 0.001), whereas obestatin to acylated ghrelin and PYY to acylated ghrelin ratios were increased in both groups with bingeing-purging behavior (P < 0.0001). Patients with AN-associated bingeing-purging behavior present a very different profile of appetite regulatory peptides when compared with the pure restrictive type. The assessment of ghrelin (and eventually obestatin) could be of particular interest for differential diagnosis. Very low ghrelin levels and increased anorexigenic to orexigenic peptide ratios suggest either a lack of adaptation to a starvation state or a higher facility to cope with undernutrition.

Dynamics of GHRH in third-ventricle cerebrospinal fluid of cattle: Relationship with serum concentrations of GH and responses to appetite-regulating peptides

Objectives were to (1) characterize the relationship of third-ventricle (IIIV) cerebrospinal fluid (CSF) concentrations of growth hormone–releasing hormone (GHRH) with concentrations of GH in the peripheral circulation; and (2) assess the influence of acute administration of appetite-regulating peptides leptin (anti-orexigenic) and neuropeptide Y (NPY; orexigenic) on the release of GHRH. Six mature beef cows fitted with IIIV and jugular vein cannulae were treated intracerebroventricularly with saline, and leptin (600 μg) and NPY (500 μg) in saline, in a replicated 3 × 3 Latin square design. Third-ventricle CSF and blood were collected 10 min before and continued 220 min after treatments. Mean concentrations of GHRH and frequency of pulses after treatments were 2.2 ± 0.13 ng/mL and 1.2 ± 0.15 pulses/220 min, respectively. These measures were not influenced by treatments. Concentrations of GHRH in CSF were weakly correlated ( r = 0.15; P < 0.03) with serum concentrations of GH; however, 58% of the GH pulses were preceded by a pulse of GHRH and 90% of the GHRH pulses occurred within 20 min preceding a pulse of GH. Leptin tended ( P < 0.10) to suppress GH area under the curve (AUC) compared to saline. Concomitantly, NPY tended ( P < 0.10) to increase GH AUC, which appeared to be a consequence of increased ( P < 0.05) pulse amplitude. Infusion of NPY also increased ( P < 0.05) AUC of GHRH relative to saline. No differences were detected among treatments in serum concentrations of insulin-like growth factor-I or its AUC. Sampling CSF from the IIIV appears to be a viable procedure for assessing hypothalamic release of GHRH coincident with anterior pituitary gland secretion of GH in cattle. These data also demonstrate the differential responsiveness of the GH axis to appetite-regulating peptides.

Differential Effects of Restricted Versus Unlimited High‐Fat Feeding in Rats on Fat Mass, Plasma Hormones and Brain Appetite Regulators

The rapid rise in obesity has been linked to altered food consumption patterns. There is increasing evidence that, in addition to total energy intake, the macronutrient composition of the diet may influence the development of obesity. The present study aimed to examine the impact of high dietary fat content, under both isocaloric and hypercaloric conditions, compared with a low fat diet, on adiposity, glucose and lipid metabolism, and brain appetite regulators in rats. Male Sprague-Dawley rats were exposed to one of three diets: control (14% fat), ad lib high-fat palatable (HFD, 35% fat) or high-fat palatable restricted (HFD-R, matched to the energy intake of control) and were killed in the fasting state 11 weeks later. Body weight was increased by 28% in unrestricted HFD fed rats, with an almost tripling of caloric intake and fat mass (P < 0.001) and double the plasma triglycerides of controls. Glucose intolerance and increased insulin levels were observed. HFD-R animals calorie matched to control had double their fat mass, plasma insulin and triglycerides (P < 0.05). Only ad lib consumption of the HFD increased the hypothalamic mRNA expression of the appetite-regulating peptides, neuropeptide Y and pro-opiomelanocortin. Although restricted consumption of palatable HFD had no significant impact on hypothalamic appetite regulators or body weight, it increased adiposity and circulating triglycerides, suggesting that the proportion of dietary fat, independent of caloric intake, affects fat deposition and the metabolic profile.

Ghrelin receptor (GHS-R)-like receptor and its genomic organisation in rainbow trout, Oncorhynchus mykiss

Ghrelin, a GH-releasing and appetite-regulating peptide that is released from the stomach is an endogenous ligand for growth hormone secretagogue-receptor (GHS-R). Two types of GHS-R are accepted to be present, a functional GHS-R1a and GHS-R1b with unknown function. In this study, we identified cDNA that encodes protein with close sequence similarity to GHS-R and exon–intron organization of the GHS-R genes in rainbow trout, Oncorhynchus mykiss. Two variants of GHS-R1a proteins with 387-amino acids, namely DQTA/LN-type and ERAT/IS-type, were identified. In 3'-RACE PCR and genomic PCR, we also identified three GHS-R1b orthologs that are consisted of 297- or 300-amino acids with different amino acid sequence at the C-terminus, in addition to the DQTA/LN-type and ERAT/IS-type variations. Genomic PCR revealed that the genes are composed of two exons separated by an intron, and that two GHS-R1a and three GHS-R1b variants are generated by three distinct genes. GHS-R1a and GHSR-1b mRNA were predominantly expressed in the pituitary, followed by the brain. Identified DQTA/LN-type or ERAT/IS-type GHS-R1a cDNA was transfected into mammalian cells, and intracellular calcium ion mobilization assay was carried out. However, we did not find any response to rat ghrelin and a homologous ligand, des-VRQ trout ghrelin, of either receptor in vitro. We found that unexpected mRNA splicing had occurred in the transfected cells, suggesting that the full-length, functional receptor protein might not be generated in the cells. Gene structure and characterization of protein sequence identified in this study were closely similar to other GHS-R, but to conclude that it is a GHS-R for rainbow trout, further study is required to confirm activation of GHS-R1a by ghrelin or GHS. Thus we designated the identified receptor proteins in this study as GHS-R-like receptor (GHSR-LR).

The effect of a high-MUFA, low-glycaemic index diet and a low-fat diet on appetite and glucose metabolism during a 6-month weight maintenance period

We aimed to test the effects of three different weight maintenance diets on appetite, glucose and fat metabolism following an initial low-energy diet (LED) induced body weight loss. Following an 8-week LED and a 2-3-week refeeding period, 131 subjects were randomized to three diets for 6 months: MUFA, moderate-fat (35-45 energy percentage (E%) fat), high in MUFA with low glycaemic index; LF, low fat (20-30 E% fat) or CTR, control (35 E% fat). A meal test study was performed in a subgroup, before and after the 6-month dietary intervention, with forty-two subjects completing both meal tests. No difference in body weight, energy intake or appetite ratings were observed between diets. Both the LF and MUFA diets compared to CTR diet reduced postprandial glycaemia and insulinaemia and lowered fasting insulin from month 0 to month 6. Following the 8-week LED period lower levels of the appetite regulating peptides, pancreatic polypeptide, peptide YY, glucagon-like peptide-1 and glucagon-like peptide-2, along with increased appetite scores were seen in comparison to measurements performed after the 6-month dietary intervention. In conclusion, the two competing diets, MUFA and LF, were equally good with respect to glucose metabolism, whereas the CTR diet resembling the typical Western diet, high in SFA, sugar and high glycaemic carbohydrates, indicated associations to lowering of insulin sensitivity. Lower levels of appetite regulatory peptides along with increased appetite scores following an 8-week LED and 2-3-week refeeding period, suggest that strategies for physiological appetite control following a LED period are needed, in order to prevent weight regain.

Endogenous prolactin-releasing peptide regulates food intake in rodents

Food intake is regulated by a network of signals that emanate from the gut and the brainstem. The peripheral satiety signal cholecystokinin is released from the gut following food intake and acts on fibers of the vagus nerve, which project to the brainstem and activate neurons that modulate both gastrointestinal function and appetite. In this study, we found that neurons in the nucleus tractus solitarii of the brainstem that express prolactin-releasing peptide (PrRP) are activated rapidly by food ingestion. To further examine the role of this peptide in the control of food intake and energy metabolism, we generated PrRP-deficient mice and found that they displayed late-onset obesity and adiposity, phenotypes that reflected an increase in meal size, hyperphagia, and attenuated responses to the anorexigenic signals cholecystokinin and leptin. Hypothalamic expression of 6 other appetite-regulating peptides remained unchanged in the PrRP-deficient mice. Blockade of endogenous PrRP signaling in WT rats by central injection of PrRP-specific mAb resulted in an increase in food intake, as reflected by an increase in meal size. These data suggest that PrRP relays satiety signals within the brain and that selective disturbance of this system can result in obesity and associated metabolic disorders.

Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader–Willi syndrome

Ghrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader-Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS. A 56-week prospective, randomized, cross-over trial. Nine subjects with PWS (age 14.6 (10.8-18.9) years, body mass index (BMI) Z-score +1.9 (0.6-3.0)) received either Oct (30 mg) or saline i.m. every 4 weeks for 16 weeks and were switched over to the other treatment after a 24-week washout period. Eight subjects completed the study. Oct caused a decrease in both acylated (-53%) and desacyl (-54%) fasting ghrelin concentrations (P<0.05) but did not significantly affect BMI. Oct had no significant effect on peptide YY concentrations, appetite or compulsive behaviour towards food. Oct caused a decrease in insulin-like growth factor-I concentrations, an increase in HbA1c and transient elevation of blood glucose in two subjects. Three subjects developed gallstones. Oct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future intervention studies aiming at clarifying the role of ghrelin in PWS should focus on the administration of specific inhibitors of ghrelin secretion or ghrelin receptor activity that do not interfere with other appetite-regulating peptides.

The putative role of neuropeptide autoantibodies in anorexia nervosa

Anorexia nervosa remains a disease of unknown etiology. This situation explains the failure to develop effective therapy and emphasizes the fact that the neurobiological mechanisms of appetite and emotion are still incompletely understood. The present review is the first summary of recent research assigning to the immune system a new role in energy and emotional regulation by the production of autoantibodies directed against neuropeptides. The results of this research are promising to shed light on the etiology of eating disorders and open new fields for biological diagnosis and follow-up as well as designing new therapeutic strategies. Following the initial identification of autoantibodies against alpha-melanocyte-stimulating hormone, a key neuropeptide involved in the regulation of satiety and mood, in the plasma of patients with anorexia and bulimia nervosa, it has been further found that the serum levels of these autoantibodies correlated with psychopathological traits in individuals with eating disorders. Furthermore, recent findings show that autoantibodies against alpha-melanocyte-stimulating hormone and against some other appetite-regulating peptide hormones are normally present in the blood of humans and rats and their production may be influenced by stress and the gut microflora. Novel data provide evidence that autoantibodies against neuropeptides can be involved in the regulation of appetite and emotion and that alteration in autoantibody-mediated signaling pathways may be responsible for the development of eating disorders.

Impaired bone health in anorexia nervosa

Anorexia nervosa (AN), a condition of malnutrition, has a multitude of effects, including low bone mineral density (BMD). Much has been discovered over the last couple of decades regarding the extent and pathophysiology of low BMD in AN, including the role of gonadal steroids, neuroendocrine hormones and appetite-regulating peptides. The effects of AN on bone are particularly concerning in adolescents, who are in the process of accruing peak bone mass, and decreased rates of bone-mass accrual in these critical years are predictive of poor bone health in later life. Although dual-energy x-ray absorptiometry continues to be the standard technique for monitoring BMD, newer techniques such as quantitative computed tomography and calcaneal ultrasound are being explored. Weight and menses recovery continue to be the most effective treatment for improving BMD in AN. Further research is needed to translate the pathophysiology being unraveled into clinical applications for improving BMD in AN.

Autoantibodies against appetite-regulating peptide hormones and neuropeptides: Putative modulation by gut microflora

Objective Peptide hormones synthesized in gastrointestinal and adipose tissues in addition to neuropeptides regulate appetite and body weight. Previously, autoantibodies directed against melanocortin peptides were found in patients with eating disorders; however, it remains unknown whether autoantibodies directed against other appetite-regulating peptides are present in human sera and whether their levels are influenced by gut-related antigens. Methods Healthy women were studied for the presence of immunoglobulin (Ig) G and IgA autoantibodies directed against 14 key appetite-regulating peptides. The concept of molecular mimicry was applied to search in silico whether bacteria, viruses, or fungi contain proteins with amino acid sequences identical to appetite-regulating peptides. In addition, autoantibodies serum levels were studied in germ-free and specific pathogen-free rats. Results We found these IgG and IgA autoantibodies directed against leptin, ghrelin, peptide YY, neuropeptide Y, and other appetite-regulating peptides are present in human sera at levels of 100–900 ng/mL. Numerous cases of sequence homology with these peptides were identified among commensal and pathogenic micro-organisms including Lactobacilli, bacteroides, Helicobacter pylori, Escherichia coli, and Candida species. Decreased levels of IgA autoantibodies directed against several appetite-regulating peptides and increased levels of antighrelin IgG were found in germ-free rats compared with specific pathogen-free rats. Conclusion Healthy humans and rats display autoantibodies directed against appetite-regulating peptide hormones and neuropeptides, suggesting that these autoantibodies may have physiologic implications in hunger and satiety pathways. Gut-related antigens including the intestinal microflora may influence production of theses autoantibodies, suggesting a new link between the gut and appetite control.

Obesity: the hormonal milieu

Obesity has reached epidemic proportions throughout the world and poses significant health and economic burdens to both developed and developing societies. Most recent data from the NHANES study (2003-2004) report that 17.1% of US children are overweight and 32.2% of adults are obese, a significant increase compared with data obtained only 6 years earlier. The neurohormonal control of appetite, body composition, and glucose homeostasis is mediated by hormones secreted from adipose tissue, endocrine glands, and enteroendocrine cells, which converge at the vagus nerve, brainstem and hypothalamus to modulate complex interactions of neurotransmitters and central appetite-regulating peptides. These hormonal signals are tightly regulated to maintain body weight/adiposity within a narrow, individually defined range that may be further impacted by variables such as ingested calories, meal composition, and lifestyle. Clinical manifestations of obesity, the metabolic syndrome and impaired glucose tolerance reflect biochemical alterations in a complex hormonal milieu. Elucidation of these hormonal perturbations in obese patients has already provided novel pharmacologic treatments to improve weight management and address the metabolic sequelae of obesity. The remarkable redundancy of these hormones, however, and their interactions make a monopharmaceutical approach unlikely to be successful.

Meal-induced compositional changes in blood and saliva in persons with bulimia nervosa

BackgroundBinge eating episodes in persons with bulimia nervosa may to some extent be a result of disturbed sensations of hunger and satiety. It has been hypothesized that abnormal appetite sensations may be due to bulimia nervosa–related alterations in the release of hormones that are known to be involved in the physiologic regulation of appetite and metabolism. ObjectiveThe objective was to investigate whether circulating concentrations of the appetite-regulating peptides leptin and ghrelin and markers of metabolism (glucose and insulin) are different in persons with bulimia nervosa than in controls before and after intake of a meal and whether these changes may be reflected in saliva. DesignTwenty women with bulimia nervosa and 20 age- and sex-matched healthy controls participated. After an overnight fast, the subjects ate a standardized carbohydrate-rich breakfast. Whole saliva and blood were collected, and visual analogue scales for hunger and satiety were completed once before and continuously for 5 h after the breakfast. ResultsA lower pre- and postprandial whole saliva flow rate was found in subjects with bulimia nervosa, which might have been attributable to a concomitant intake of potentially xerogenic medication. Subjects with bulimia nervosa experienced reduced hunger, which could not be explained by pre- or postprandial alterations in circulating ghrelin, leptin, insulin, or glucose concentrations. ConclusionsThere were no apparent differences in the composition of blood and saliva between bulimia nervosa and control subjects, and meal-induced compositional changes in blood were not directly mirrored in saliva composition.