Evaluation of the Use of Appetite Stimulants in Pediatric Patients with Cystic Fibrosis.

OBJECTIVE: Poor nutrition in patients with cystic fibrosis (CF) has been associated with lower lung function and increased morbidity and mortality. Conversely, better nutritional status has been associated with improved pulmonary function and fewer CF-associated complications. There is no consensus regarding appetite stimulant therapy in patients with CF (pwCF). The primary objective of this study was to determine if the use of appetite stimulants was associated with weight changes in pediatric pwCF in the ambulatory care setting. METHODS: This was a retrospective study that evaluated 62 pediatric pwCF who received cyproheptadine or mirtazapine for appetite stimulation for at least 6 consecutive months. Weight z scores were collected for each patient at baseline, 3, 6, and 12 months of therapy, if available. RESULTS: Increase in weight z score after 3 months of therapy was statistically significant based on both univariable and multivariable models when evaluating the entire cohort. The adjusted mean difference for change in weight z score was 0.33 ( P < 0.001) from baseline to month 3. There was a statistically significant improvement in pulmonary function after 3 and 6 months of therapy. CONCLUSIONS: Appetite stimulant therapy was associated with improvement in weight z score in the first 3 months of treatment. Appetite stimulant therapy was associated with improvement in pulmonary function in the first 3 months of therapy, which supports the relationship between weight gain and improved pulmonary function in pwCF. These findings suggest that appetite stimulants contribute to weight gain in pediatric pwCF, particularly within the first 3 months of therapy.

Cannabinoids: the lows and the highs of chemotherapy-induced nausea and vomiting.

Despite remaining one of the most widely abused drugs worldwide, Cannabis sativa exhibits remarkable medicinal properties. The phytocannabinoids, cannabidiol and Δ-9-tetrahydrocannabinol, reduce nausea and vomiting, particularly during chemotherapy. This is attributed to their ability to reduce the release of serotonin from enterochromaffin cells in the small intestine, which would otherwise orchestrate the vomiting reflex. Although there are many preclinical and clinical studies on the effects of Δ-9-tetrahydrocannabinol during nausea and vomiting, little is known about the role that cannabidiol plays in this scenario. Since cannabidiol does not induce psychotropic effects, in contrast to other cannabinoids, its use as an anti-emetic is of great interest. This review aims to summarize the available literature on cannabinoid use, with a specific focus on the nonpsychotropic drug cannabidiol, as well as the roles that cannabinoids play in preventing several other adverse side effects of chemotherapy including organ toxicity, pain and loss of appetite.

Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review.

OBJECTIVE: A systematic review identifying the use of cyproheptadine (CY) as an appetite stimulant was completed. METHOD: Studies of any design exploring the efficacy of CY as an appetite stimulant in all age groups and populations were included. Primary outcomes of studies included were weight gain, appetite stimulation, and/or caloric/nutritional intake increase. The review was completed in accordance with PRISMA standards. RESULTS: A total of 46 articles across 21 different treatment populations met criteria for the review, including 32 randomized controlled trials, 4 prospective cohort studies, 4 retrospective cohort studies, 4 case reports and 2 case series. Of these, 39 demonstrated that CY resulted in significant weight gain in the sample under study. Studies exploring the use of CY in those with malignant/progressive disease states, such as HIV and cancer, showed minimal to no benefit of the medication. Transient mild to moderate sedation was the most commonly reported side effect. Studies included were heterogeneous in terms of methods as well as study patient demographics, characteristics and concurrent medical conditions. Few studies provided objective measures of appetite change. DISCUSSION: CY appears to be a safe, generally well-tolerated medication that has utility in helping facilitate weight gain in patients drawn from a variety of underweight populations. Future prospective randomized controlled studies in low weight patients that include objective measures of appetite and intake are needed to better understand the mechanism by which CY augments weight gain.

Interaction of the dopaminergic and Nociceptin/Orphanin FQ on central feed intake regulation in chicken.

1. The aim of the current study was to determine the effects of the central dopaminergic system on N/OFQ-induced feed intake in 3-h feed-deprived neonatal broilers. 2. In experiment 1, chicken received intracerebroventricular (ICV) injections of a control solution, SCH 23 390 (D1 receptors antagonist, 5 nmol), N/OFQ (16 nmol) or their combination (SCH23 390 + N/OFQ). In experiment 2, a control solution, AMI-193 (D2 receptors antagonist, 5 nmol), N/OFQ (16 nmol) or their combination (AMI-193 + N/OFQ) were ICV injected into chickens. In experiment 3, birds received ICV injections of a control solution, NGB2904 (D3 receptors antagonist, 6.4 nmol), N/OFQ (16 nmol) and co-injection of NGB2904 + N/OFQ. In experiment 4, ICV injections of the control solution, L-741,742 (D4 receptors antagonist, 6 nmol), N/OFQ (16 nmol) or their combination (L-741,742 + N/OFQ) were applied to broilers. In experiment 5, birds were ICV injected with control solution, L-DOPA (dopamine precursor, 125 nmol), N/OFQ (16 nmol) and L-DOPA + N/OFQ. Cumulative feed intake was recorded until 120 min after injection. 3. According to the results, ICV injection of N/OFQ significantly increased feed intake (P < 0.05). Co-injection of N/OFQ and D1 receptor antagonist (SCH 23390) amplified hyperphagic effect of N/OFQ (P < 0.05). The N/OFQ-induced feed intake was increased by the D2 receptor antagonist (P < 0.05). The hyperphagic effect of N/PFQ was weakened by co-injection of L-DOPA + N/OFQ (P < 0.05). 4. These results suggested that an interaction exists between dopamine and N/OFQ via D1 and D2 receptors on central feed intake in neonatal broiler chickens.

A cannabigerol-rich Cannabis sativa extract, devoid of [INCREMENT]9-tetrahydrocannabinol, elicits hyperphagia in rats.

Nonpsychoactive phytocannabinoids (pCBs) from Cannabis sativa may represent novel therapeutic options for cachexia because of their pleiotropic pharmacological activities, including appetite stimulation. We have recently shown that purified cannabigerol (CBG) is a novel appetite stimulant in rats. As standardized extracts from Cannabis chemotypes dominant in one pCB [botanical drug substances (BDSs)] often show greater efficacy and/or potency than purified pCBs, we investigated the effects of a CBG-rich BDS, devoid of psychoactive [INCREMENT]-tetrahydrocannabinol, on feeding behaviour. Following a 2 h prefeed satiation procedure, 16 male Lister-hooded rats were administered CBG-BDS (at 30-240 mg/kg) or vehicle. Food intake, meal pattern microstructure and locomotor activity were recorded over 2 h. The total food intake was increased by 120 and 240 mg/kg CBG-BDS (1.53 and 1.36 g, respectively, vs. 0.56 g in vehicle-treated animals). Latency to feeding onset was dose dependently decreased at all doses, and 120 and 240 mg/kg doses increased both the number of meals consumed and the cumulative size of the first two meals. No significant effect was observed on ambulatory activity or rearing behaviour. CBG-BDS is a novel appetite stimulant, which may have greater potency than purified CBG, despite the absence of [INCREMENT]-tetrahydrocannabinol in the extract.

The role of 5-HT2c receptor on corticosterone-mediated food intake.

Corticosterone plays an important role in feeding behavior. However, its mechanism remains unclear. Therefore, the present study aimed to investigate the effect of corticosterone on feeding behavior. In this study, cumulative food intake was increased by acute corticosterone administration in a dose-dependent manner. Administration of the 5-HT2c receptor agonist m-chlorophenylpiperazin (mCPP) reversed the effect of corticosterone on food intake. The anorectic effects of mCPP were also blocked by the 5-HT2c receptor antagonist RS102221 in corticosterone-treated mice. Both corticosterone and mCPP increased c-Fos expression in hypothalamic nuclei, but not the nucleus of the solitary tract. RS102221 inhibited c-Fos expression induced by mCPP, but not corticosterone. In addition, mCPP had little effect on TH and POMC levels in the hypothalamus. Furthermore, mCPP antagonized decreasing effect of the leptin produced by corticosterone. Taken together, our findings suggest that 5-HT2c receptors and leptin may be involved in the effects of corticosterone-induced hyperphagia.

Capromorelin oral solution (ENTYCE®) increases food consumption and body weight when administered for 4 consecutive days to healthy adult Beagle dogs in a randomized, masked, placebo controlled study.

BACKGROUND: Dogs can suffer from inappetence caused by a variety of medical conditions. This may present as anorexia (complete loss of appetite), hyporexia (decreased appetite) or dysrexia (change in food preferences). A drug with a new mechanism of action, capromorelin, has potential to stimulate appetite in dogs. Capromorelin is a ghrelin receptor agonist, which mimics the action of endogenous ghrelin. It is a member of the growth hormone secretagogue (GHS) class of drugs. Capromorelin oral solution (ENTYCE®) was tested in healthy adult male and female Beagle dogs (n = 6 males and 6 females per group) for its effect on food consumption and body weight. A randomized, masked, placebo controlled study was conducted to measure the effects of a daily 3 mg/kg oral dose given over 4 days. Dogs were observed for clinical signs, physical examinations were completed prior to and at the end of treatment, and blood was drawn before and after treatment for evaluation of serum chemistry and hematology parameters. RESULTS: Capromorelin was well-tolerated, with no abnormalities seen on physical examination or clinical pathology. Some dogs showed increased salivation. Capromorelin treated dogs had increased mean (±SD) food consumption compared to placebo treated dogs (60.55 ± 39.87% versus -11.15 ± 14.23% respectively, P < 0.001). Treated dogs also had increased mean body weights compared to placebo treated dogs (5.96 ± 1.76% versus 0.053 ± 1.14% respectively, P < 0.001). CONCLUSIONS: This study supports the effectiveness of capromorelin oral solution as an appetite stimulant in dogs. Treatment with the oral solution resulted in dramatic increases in appetite, as measured by food consumption, of over 60% compared to placebo. The drug was well tolerated. Capromorelin is the first ghrelin receptor agonist developed for appetite stimulation in any species, and represents a novel mechanism of action for this clinical use.

Evaluation of the safety in dogs of long-term, daily oral administration of capromorelin, a novel drug for stimulation of appetite.

The objective of the study was to evaluate the safety of capromorelin, a ghrelin agonist that stimulates appetite and causes increased body weight and the release of growth hormone (GH). Beagle dogs (n = 32) received either oral placebo or 0.3, 7, or 40 mg/kg capromorelin once daily for 12 consecutive months. Safety was evaluated by physical examinations, including ECG and ophthalmic examinations, and comprehensive clinical pathology. Serum levels of capromorelin, GH, and insulin-like growth factor 1 (IGF-1) were measured periodically. Necropsies and histopathological evaluations were performed at study termination. As expected, GH and IGF-1 levels were mildly increased in capromorelin-treated dogs. Adverse events were limited to mild emesis and loose stools in all groups and excess salivation among some dogs receiving higher capromorelin doses. Clinical pathology testing was generally normal, although blood lipids and alkaline phosphatase levels were moderately increased among dogs receiving capromorelin. Treated dogs had slightly longer post-treatment PR intervals seen on ECG, but with no changes in cardiac histopathology. Postmortem findings were normal. Drug-related increases in liver weight were linked to overall increases in body weight. Capromorelin was well tolerated in dogs at daily doses up to 40 mg/kg for 12 months, demonstrating a wide safety margin.

Appetite-Enhancing Effects of Curry Oil.

Inhalation of scent compounds with phenylpropanoidal structures, such as trans-cinnamaldehyde, is expected to increase the appetite. The scent of curry powder is well known for its appetite-enhancing effect on humans. In this work, we show that the appetite of mice after inhalation of curry powder essential oil or benzylacetone showed a similar increase. The components of curry oil, trans-cinnamaldehyde, trans-anethole, and eugenol, each showed appetite-enhancing effects; therefore, these three scent compounds may be the active compounds in curry powder oil.

Appetite-Enhancing Effects: The Influence of Concentrations of Benzylacetone and trans-Cinnamaldehyde and Their Inhalation Time, as Well as the Effect of Aroma, on Body Weight in Mice.

Benzylacetone has appetite-enhancing and locomotor-reducing effects. The effective doses for these two outcomes overlap, and the weight gain of mice exposed to benzylacetone is caused by both appetite-enhancement and a reduction in locomotor activity. The appetite-enhancing effects of trans-cinnamaldehyde and benzylacetone have been reported previously. In this study, these appetite-enhancing effects were seen in mice after short-term, high-dose exposure.

Implication of coronin 7 in body weight regulation in humans, mice and flies.

BACKGROUND: Obesity is a growing global concern with strong associations with cardiovascular disease, cancer and type-2 diabetes. Although various genome-wide association studies have identified more than 40 genes associated with obesity, these genes cannot fully explain the heritability of obesity, suggesting there may be other contributing factors, including epigenetic effects. RESULTS: We performed genome wide DNA methylation profiling comparing normal-weight and obese 9-13 year old children to investigate possible epigenetic changes correlated with obesity. Of note, obese children had significantly lower methylation levels at a CpG site located near coronin 7 (CORO7), which encodes a tryptophan-aspartic acid dipeptide (WD)-repeat containing protein most likely involved in Golgi complex morphology and function. Anatomical profiling of coronin 7 (Coro7) mRNA expression in mice revealed that it is highly expressed in appetite and energy balance regulating regions, including the hypothalamus, striatum and locus coeruleus, the main noradrenergic brain site. Interestingly, we found that food deprivation in mice downregulates hypothalamic Coro7 mRNA levels, and injecting ethanol, an appetite stimulant, increased the number of Coro7 expressing cells in the locus coeruleus. Finally, by employing the genetically-tractable Drosophila melanogaster model we were able to demonstrate an evolutionarily conserved metabolic function for the CORO7 homologue pod1. Knocking down the pod1 in the Drosophila adult nervous system increased their resistance to starvation. Furthermore, feeding flies a high-calorie diet significantly increased pod1 expression. CONCLUSION: We conclude that coronin 7 is involved in the regulation of energy homeostasis and this role stems, to some degree, from the effect on feeding for calories and reward.

Dietary Macronutrient Composition Affects the Influence of Exogenous Prolactin-Releasing Peptide on Appetite Responses and Hypothalamic Gene Expression in Chickens.

BACKGROUND: The interaction between the effects of exogenous neurotransmitters and dietary composition on appetite regulation in nonmammalian species is unclear. OBJECTIVE: The objective of this study was to determine the effects of exogenous prolactin-releasing peptide (PrRP) and dietary macronutrient composition on food intake regulation in broiler chicks. METHODS: Three isocaloric diets were formulated: high-carbohydrate (HC), high-fat (HF; 60% of ME from lard) and high-protein (HP) diets. In Expt. 1, 4-d-old Hubbard × Cobb-500 chicks fed 1 of the 3 diets since hatch were intracerebroventricularly injected with 0 (vehicle), 3, or 188 pmol PrRP (n = 10). Food intake was measured for 180 min. In Expt. 2, hypothalamic mRNA abundance of appetite-associated factors was measured in hypothalamus samples obtained 1 h postinjection of 0 or 188 pmol PrRP. In Expt. 3, chicks were given free access to all diets before and after intracerebroventricular injection and food intake was measured. RESULTS: Three and 188 pmol PrRP increased (P = 0.0008 and 0.04) HP diet intake, but only 188 pmol PrRP was efficacious at increasing HC (P = 0.0011) and HF (P = 0.01) consumption compared with the vehicle. There was a diet effect on mRNA abundance of all genes (P < 0.05), with greater expression in chicks fed the HF or HP than the HC diet. Whereas neuropeptide Y (NPY) mRNA was similar between vehicle- and PrRP-injected chicks that consumed HP or HF diets, expression was greater (P < 0.05) in PrRP- than vehicle-injected chicks that consumed the HC diet. When chicks had access to all diets, 188 pmol PrRP caused preferential (P < 0.0001) intake of the HP over the HC and HF diets. CONCLUSION: The HP diet enhanced the sensitivity of chicks to the food intake-stimulating effects of PrRP, and PrRP in turn increased preference for the HP diet. Thus, dietary macronutrient composition influences PrRP-mediated food intake, and PrRP in turn affects nutrient intake and transcriptional regulation in chicks.

Feeding stimulants for larvae of Graphium sarpedon nipponum (Lepidoptera: Papilionidae) from Cinnamomum camphora.

The feeding response of larvae of the swallowtail butterfly, Graphium sarpedon nipponum (Lepidoptera: Papilionidae), is elicited by a methanolic extract from camphor tree (Cinnamomum camphora) leaves. Based on bioassay-guided fractionation, three compounds, isolated from the methanolic extract of fresh leaves of the camphor tree, were revealed to be involved in a multi-component system of feeding stimulants. Structures of these feeding stimulants were identified as sucrose, 5-O-caffeoylquinic acid and quercetin 3-O-ß-glucopyranoside by NMR and LC-MS.

Use of cyproheptadine in young children with feeding difficulties and poor growth in a pediatric feeding program.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of cyproheptadine (CY) use in infants and young children with poor growth treated at our multidisciplinary pediatric feeding program, and to describe changes in their weight and feeding behaviors. METHODS: A retrospective chart review of children treated with CY from January 2007 to July 2011 was performed. Demographic data, medical diagnosis, adverse effects of the drug, and changes in mealtime behaviors were extracted from the patients' medical records. For each patient who received the CY, weight-for-age z scores (WtZ) were calculated before and during treatment. Repeated-measures mixed model was used to analyze the pattern of change in WtZ over time and between groups. Differences in mean WtZ were tested between patients regularly receiving CY and a naturally conceived comparison group. RESULTS: Of the 127 patients in treatment owing to poor weight gain who received the CY, 82 took the medication regularly as prescribed in combination with our interventional program. For these patients, the majority of the parents (96%) reported a positive change in mealtime and feeding behaviors. A significant improvement in mean WtZ was observed after starting CY when compared with the WtZ before treatment for those patients regularly receiving the medication. This effect was independent of patients' age and/or presence of an underline medical problem. No significant differences in mean WtZ were observed over time within the comparison group. CONCLUSIONS: In our experience, the use of CY in combination with a specialized multidisciplinary interventional program is a safe and effective therapy in infants and young children with low appetite and poor growth.

Evaluating the Safety and Efficacy of Capromorelin in Rhesus Macaques (Macaca mulatta).

Nonhuman primates used in biomedical research may experience clinically significant weight loss for a variety of reasons. Episodes of anorexia (complete loss of appetite) or hyporexia (decreased appetite) can result in significant weight loss, potentially altering animal welfare and scientific studies. The FDA has approved several appetite stimulants for use in domestic species, but currently none are approved for use in NHP. Treatment of inappetence and weight loss in NHP often relies on the extralabel use of these compounds. Capromorelin is a ghrelin receptor agonist. As a growth hormone secretagogue, capromorelin increases appetite, leading to weight gain. Studies in several species have shown a positive correlation between capromorelin administration and weight gain; in 2017, an oral solution of capromorelin received FDA approval for use in dogs. We tested this solution in healthy adult rhesus macaques (n = 3 males and 3 females) for its effects on body weight and insulin like growth factor-1 (IGF-1). A control group (n = 2 males and 2 females) was used for comparison. Treated macaques received a 3mg/kg oral dose daily for 7 d. Clinical signs were observed daily. Weights were collected before, during and at the end of treatment. Blood was drawn before, during and after treatment for measurement of IGF-1 levels and standard hematology and biochemistry parameters. Baseline-adjusted mean body weights and IGF-1 levels were significantly higher in treated as compared with control monkeys after 7 d of beginning treatment (body weight of 10.5±0.1kg (mean ± SEM) and 10.1±0.1kg, respectively; IGF-1 of 758±43ng/mL and 639±22ng/mL, respectively). Capromorelin administration was not associated with appreciable changes in hematologic and biochemical values in treated macaques. These findings suggest that capromorelin may be useful for treating inappetence and weight loss in NHP, and based on blood analysis, a 7-d course of treatment does not appear to cause acute toxicity.

Goldfish spexin: solution structure and novel function as a satiety factor in feeding control.

Spexin (SPX) is a neuropeptide identified recently by bioinformatic approach. At present not much is known about its biological actions, and comparative studies of SPX in nonmammalian species are still lacking. To examine the structure and function of SPX in fish model, SPX was cloned in goldfish and found to be highly comparable with its mammalian counterparts. As revealed by NMR spectroscopies, goldfish SPX is composed of an α-helix from Gln(5) to Gln(14) with a flexible NH2 terminus from Asn(1) to Pro(4), and its molecular surface is largely hydrophobic except for Lys(11) as the only charged residue in the helical region. In goldfish, SPX transcripts were found to be widely expressed in various tissues, and protein expression of SPX was also detected in the brain. In vivo feeding studies revealed that SPX mRNA levels in the telencephalon, optic tectum, and hypothalamus of goldfish brain could be elevated by food intake. However, brain injection of goldfish SPX inhibited both basal and NPY- or orexin-induced feeding behavior and food consumption. Similar treatment also reduced transcript expression of NPY, AgRP, and apelin, with concurrent rises in CCK, CART, POMC, MCH, and CRH mRNA levels in different brain areas examined. The differential effects of SPX treatment on NPY, CCK, and MCH transcript expression could also be noted in vitro in goldfish brain cell culture. Our studies for the first time unveil the solution structure of SPX and its novel function as a satiety factor through differential modulation of central orexigenic and anorexigenic signals.

Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study.

PURPOSE: Cachexia in cancer adversely affects patients' perception of symptoms, well-being, and response to therapy, and shortens survival. Anamorelin, an oral mimetic of ghrelin, has been shown to increase body weight and anabolic hormone levels in healthy volunteers and is being investigated to treat cancer cachexia. METHODS: This multicenter, double-blind, placebo-controlled, crossover study evaluated the effects of anamorelin in 16 patients with different cancers and cachexia. Patients were randomly assigned to anamorelin 50 mg/day or placebo for 3 days. A 3- to 7-day washout period followed and then treatments were switched. Assessments included body weight, appetite, food intake, growth hormone (GH) levels, patient-reported symptom assessments (e.g., the Anderson Symptom Assessment Scale [ASAS] and also an inclusion criterion), and safety. RESULTS: Anamorelin significantly increased body weight compared with placebo (0.77 kg vs. -0.33 kg). Food intake increased compared with placebo, but not significantly. GH significantly increased at all time points (0.5-4 h postdose). Insulin-like growth factor-1 (IGF-1) significantly increased by 54.09 ng/mL with anamorelin treatment compared with -3.56 ng/mL for placebo; significant changes in insulin-like growth factor-binding protein 3 (IGFBP-3) were 0.75 µg/mL vs. -0.19 µg/mL, respectively. Patient-reported symptoms, including appetite as measured by ASAS, significantly improved with anamorelin (8.1 vs. 1.0 for placebo). Adverse events (AEs) in four patients were possibly or probably related to anamorelin: hyperglycemia (two patients), nausea (one patient), and dizziness (one patient). Most AEs were mild; no patients withdrew due to AEs. CONCLUSIONS: Anamorelin showed significant metabolic, clinical, and patient-rated effects in cancer cachexia. Further studies are warranted.

Exogenous peptide YY3-36 and Exendin-4 further decrease food intake, whereas octreotide increases food intake in rats after Roux-en-Y gastric bypass.

BACKGROUND: Patients show an elevated postprandial satiety gut hormone release after Roux-en-Y Gastric bypass (gastric bypass). The altered gut hormone response appears to have a prominent role in the reduction of appetite and body weight (BW) after gastric bypass. Patients with insufficient BW loss after gastric bypass have an attenuated postprandial gut hormone response in comparison with patients who lost an adequate amount of BW. The effects of additional gut hormone administration after gastric bypass are unknown. METHODS: The effects of peripheral administration of peptide YY3-36 (PYY3-36; 300 nmol kg(-1)), glucagon-like peptide-1 (GLP-1) analogue Exendin-4 (20 nmol kg(-1)) and somatostatin analogue octreotide (10 µg kg(-1)) on feeding and BW were evaluated in rats after gastric bypass. RESULTS: Gastric bypass rats weighed (P<0.01) and ate less on postoperative day 5 (P<0.001) and thereafter, whereas postprandial plasma PYY and GLP-1 levels were higher compared with sham-operated controls (P<0.001). Administration of both PYY3-36 and Exendin-4 led to a further decrease in food intake in bypass rats compared with saline treatment (P=0.02 and P<0.0001, respectively). Similar reduction in food intake was observed in sham rats (P=0.02 and P<0.001, respectively). Exendin-4 treatment resulted in a significant BW loss in bypass (P=0.03) and sham rats (P=0.04). Subsequent treatment with octreotide led to an increase in food intake in bypass (P=0.007), but not in sham rats (P=0.87). CONCLUSION: Peripheral administration of PYY3-36 and Exendin-4 reduces short-term food intake, whereas octreotide increases short-term food intake in rats after gastric bypass. The endogenous gut hormone response after gastric bypass can thus potentially be further enhanced by additional exogenous therapy with pharmacological doses of gut hormones in patients with insufficient weight loss or weight regain after surgery.