peptide YY |
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CHEBI:80330 |
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A 36-membered human gut polypeptide consisting of Tyr, Pro, Ile, Lys, Pro, Glu, Ala, Pro, Gly, Glu, Asp, Ala, Ser, Pro, Glu, Glu, Leu, Asn, Arg, Tyr, Tyr, Ala, Ser, Leu, Arg, His, Tyr, Leu, Asn, Leu, Val, Thr, Arg, Gln, Arg and Tyr-NH2 residues joined in sequence. |
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This entity has been manually annotated by the ChEBI Team.
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Peptide YY (PYY), also known as peptide tyrosine tyrosine, is a peptide that in humans is encoded by the PYY gene. Peptide YY is a short (36-amino acid) peptide released from cells in the ileum and colon in response to feeding. In the blood, gut, and other elements of periphery, PYY acts to reduce appetite; similarly, when injected directly into the central nervous system, PYY is also anorexigenic, i.e., it reduces appetite.
Dietary fibers from fruits, vegetables, and whole grains, consumed, increase the speed of transit of intestinal chyme into the ileum, to raise PYY3-36, and induce satiety. Peptide YY cannot be produced as the result of enzymatic breakdown of crude fish proteins and ingested as a food product.
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Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
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neuropeptide Y2 receptor agonist
An agonist that binds to and activates neuropeptide Y2 receptors.
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
hormone
Originally referring to an endogenous compound that is formed in specialized organ or group of cells and carried to another organ or group of cells, in the same organism, upon which it has a specific regulatory function, the term is now commonly used to include non-endogenous, semi-synthetic and fully synthetic analogues of such compounds.
(via peptide hormone )
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appetite depressant
Any agent that is used to decrease appetite.
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View more via ChEBI Ontology
peptide tyrosine tyrosine
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ChEBI
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PYY (3-36)
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ChEBI
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PYY 3-36
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ChEBI
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PYY3-36
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ChEBI
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Tyr-Pro-Ile-Lys-Pro-Glu-Ala-Pro-Gly-Glu-Asp-Ala-Ser-Pro-Glu-Glu-Leu-Asn-Arg-Tyr-Tyr-Ala-Ser-Leu-Arg-His-Tyr-Leu-Asn-Leu-Val-Thr-Arg-Gln-Arg-Tyr-NH2
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ChEBI
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YPIKPEAPGEDASPEELNYYASLRHYLNLVTRQRY-NH2
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ChEBI
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1366182-03-7
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CAS Registry Number
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ChemIDplus
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9754261
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Reaxys Registry Number
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Reaxys
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Nishizawa N, Niida A, Masuda Y, Kumano S, Yokoyama K, Hirabayashi H, Amano N, Ohtaki T, Asami T (2017) Antiobesity Effect of a Short-Length Peptide YY Analogue after Continuous Administration in Mice. ACS medicinal chemistry letters 8, 628-631 [PubMed:28626523] [show Abstract] Gastrointestinal peptides such as peptide YY (PYY) can regulate appetite, which is relevant to the study of obesity. The intraperitoneal bolus administration of PYY3-36 and a 12-amino acid PYY analogue, benzoyl-[Cha27,28,36,Aib31]PYY25-36 (1), showed similar anorectic activity by activating the Y2 receptor (Y2R). However, food intake inhibition and body weight loss were not observed upon continuous subcutaneous administration of 1 with osmotic pumps in diet-induced obese (DIO) mice. N-Terminal elongation of 1, together with amino acid substitution at position 24, led to a hydrophilic 14-amino acid peptide, Ac-[d-Hyp24,Cha27,28,36,Aib31]PYY23-36 (18), that showed higher affinity and more potent agonist activity for Y2R and a robust anorectic activity with potency similar to that of PYY3-36. In addition, the continuous subcutaneous administration of 18 at 0.3 mg/(kg·day) induced significant body weight loss in DIO mice. These results suggest that a short-length PYY analogue can be a lead compound for antiobesity therapy in a sustained-release formulation. | Reverri EJ, Randolph JM, Kappagoda CT, Park E, Edirisinghe I, Burton-Freeman BM (2017) Assessing beans as a source of intrinsic fiber on satiety in men and women with metabolic syndrome. Appetite 118, 75-81 [PubMed:28735851] [show Abstract] Dietary fiber is well-known for its satiety inducing properties. Adding fibers to mixed dishes is one way to increase fiber intake. However, adding fibers to foods versus including foods inherently containing fiber may reveal differing effects on satiety. The present study aimed to explore the satiety effects of adding fiber to a mixed meal versus using beans (Phaseolus vulgaris) as a source of intrinsic fiber in the meal. In this pilot study, 12 men and women with metabolic syndrome were randomly assigned to eat three standard meals in a crossover design on three different occasions that contained either no added fiber (control (NF)), extrinsic or added fiber (AF), or whole black beans as the source of intrinsic fiber (BN). Meals were matched for energy and macronutrient composition. Five hour postprandial subjective satiety was measured along with blood glucose, insulin, and the GI hormones, cholecystokinin (CCK) and peptide tyrosine tyrosine (PYY3-36). All meals induced fullness to a similar degree; however, the AF meal suppressed prospective consumption (F2,187 = 9.05, P = 0.0002) compared to the BN or NF meals. The NF meal tended to result in more satisfaction than the BN meal (F2,187 = 5.91, P = 0.003). The BN meal produced significantly higher postprandial CCK concentrations compared to the AF (F2,187 = 6.82, P = 0.001) and NF meals (F2,187 = 6.82, P = 0.002). Similar findings were observed for PYY3-36 response for BN > AF meal (F2,170 = 9.11, P < 0.0001). Postprandial insulin was significantly reduced after the BN meal, compared to the NF (F2,187 = 22.36, P < 0.0001) meal. These findings suggest that incorporating whole black beans into a meal has acute beneficial metabolic and GI hormone responses in adults with metabolic syndrome and are preferred over adding equivalent amounts of fiber from a supplement. | Nishizawa N, Niida A, Adachi Y, Masuda Y, Kumano S, Yokoyama K, Asakawa T, Hirabayashi H, Amano N, Takekawa S, Ohtaki T, Asami T (2017) Potent antiobesity effect of a short-length peptide YY-analogue continuously administered in mice. Bioorganic & medicinal chemistry letters 27, 3829-3832 [PubMed:28684122] [show Abstract] The gastrointestinal peptide, peptide YY3-36 (PYY3-36) and its shorter peptide analogues have been reported to reduce appetite by activating the neuropeptide Y2 receptor (Y2R), which is associated with obesity and other metabolic diseases. A 14-amino acid PYY analogue, Ac-[d-Pro24,Cha27,28,36,Aib31]PYY(23-36) (3), showed high binding affinity and agonist activity for the Y2R, similar to that of PYY3-36, but had weak anorectic activity upon continuous administration in lean mice. Three amino acid substitutions [Pya(4)26, Aib28, Lys30], which contributed to the decreased hydrophobicity of 3, efficiently increased its anorectic activity. The compound containing these three amino acids, Ac-[d-Pro24,Pya(4)26,Cha27,36,Aib28,31,Lys30]PYY(23-36) (22), exerted more potent and durable food intake suppression than that by PYY3-36 in lean mice, as well as excellent Y2R agonist activity (EC50: 0.20nM) and good subcutaneous bioavailability (66.6%). The 11-day continuous administration of 22 at 1mg/kg/day successfully produced antiobese and antidiabetic effects, with more than 20% body weight loss in obese and Type 2 diabetes ob/ob model mice. | Shi YC, Ip CK, Reed F, Sarruf DA, Wulff BS, Herzog H (2017) Y5 receptor signalling counteracts the anorectic effects of PYY3-36 in diet-induced obese mice. Journal of neuroendocrinology 29, [PubMed:28485050] [show Abstract] Peptide YY 3-36 (PYY3-36) is known as a critical satiety factor that reduces food intake both in rodents and humans. Although the anorexic effect of PYY3-36 is assumed to be mediated mainly by the Y2 receptor, the involvement of other Y-receptors in this process has never been conclusively resolved. Amongst them, the Y5 receptor (Y5R) is the most likely candidate to also be a target for PYY3-36, which is considered to counteract the anorectic effects of Y2R activation. In the present study, we show that short-term treatment of diet-induced obese wild-type (WT) and Y5R knockout mice (Y5KO) with PYY3-36 leads to a significantly reduced food intake in both genotypes, which is more pronounced in Y5R KO mice. Interestingly, chronic PYY3-36 infusion via minipumps to WT mice causes an increased cumulative food intake, which is associated with increased body weight gain. By contrast, lack of Y5R reversed this effect. Consistent with the observed increased body weight and fat mass in WT-treated mice, glucose tolerance was also impaired by chronic PYY3-36 treatment. Again, this was less affected in Y5KO mice, suggestive of a role of Y5R in the regulation of glucose homeostasis. Taken together, our data suggest that PYY3-36 mediated signalling via Y5 receptors may counteract the anorectic effects that it mediates via the Y2 receptor (Y2R), consequently lowering bodyweight in the absence of Y5 signalling. These findings open the potential of combination therapy using PYY3-36 and Y5R antagonists to enhance the food intake reducing effects of PYY3-36. | Saito R, Sonoda S, Ueno H, Motojima Y, Yoshimura M, Maruyama T, Hashimoto H, Tanaka K, Yamamoto Y, Kusuhara K, Ueta Y (2017) Involvement of central nesfatin-1 neurons on oxytocin-induced feeding suppression in rats. Neuroscience letters 655, 54-60 [PubMed:28684238] [show Abstract] Peripheral anorectic hormones, such as peptide YY (PYY) and oxytocin (OXT), suppress food intake. A newly identified anorectic neuropeptide, nesfatin-1, is synthesized in both peripheral tissue and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. Here, we examined the effects of intraperitoneal (ip) administration of PYY3-36, OXT, and OXT analog, on nesfatin-1-immunoreactive (ir) neurons in the rat hypothalamus and brainstem, using Fos double fluorescence-immunohistochemistry. The ip administration of OXT and OXT analog significantly increased the number of nesfatin-1-ir neurons expressing Fos-ir in the paraventricular nucleus, the arcuate nucleus, and the nucleus tractus solitarius, but not in the supraoptic nucleus, the lateral hypothalamic area, and the area postrema. No differences in the percentage of nesfatin-1-ir neurons expressing Fos in the nuclei of the hypothalamus and brainstem were observed, between rats treated with vehicle or those treated with PYY3-36. The decreased food intake, induced by OXT and OXT analog, was attenuated significantly by pretreatment with intracerebroventricular administration of antisense nesfatin-1. These results suggested that nesfatin-1-expressing neurons in the hypothalamus and brainstem may play a role in sensing the peripheral level of OXT and its suppression of feeding in rats. | Steinert RE, Feinle-Bisset C, Asarian L, Horowitz M, Beglinger C, Geary N (2017) Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB. Physiological reviews 97, 411-463 [PubMed:28003328] [show Abstract] The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials. | Yamaguchi E, Yasoshima Y, Shimura T (2017) Systemic administration of anorexic gut peptide hormones impairs hedonic-driven sucrose consumption in mice. Physiology & behavior 171, 158-164 [PubMed:28040488] [show Abstract] A number of reports suggest that gut hormones such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY(3-36) (PYY3-36), which are released postprandially, suppress homeostatic food intake and result in satiety and the termination of feeding. However, it remains unclear whether these peptide hormones also suppress non-homeostatic consumption of palatable foods or fluids. To examine whether gut hormones reduce hedonically motivated sugar consumption, we assessed the effects of intraperitoneal administration of these gut hormones on the consumption of a highly palatable sucrose solution, using a mouse model we previously established for binge-like sucrose overconsumption (Yasoshima and Shimura, 2015). To reduce homeostatic hunger, chow was available at nighttime prior to testing. After a limited-access training procedure for 10days, during which access to both sucrose and chow were controlled, on the test day, control mice injected with saline consumed significantly more sucrose than during the pre-training period. In contrast, sucrose consumption on the test day in the mice injected with CCK-8 (2 and 4μg/kg), GLP-1 (500 and 1000nmol/kg), or PYY3-36 (12.5 and 25nmol/kg) was significantly less than that in saline-injected mice. In a separate cohort of mice, the higher doses of CCK-8 and GLP-1 and a greater dose of PYY3-36 (50nmol/kg) did not produce conditioned taste aversion to saccharin, suggesting that the doses of exogenous hormones in the present study do not cause aversive visceral distress. The present findings suggest that the systemic administration of these three gut hormones suppresses hedonic-driven sugar consumption due to the anorexic, but not aversive-visceral, effects of these hormones. | Hassan AM, Jain P, Mayerhofer R, Fröhlich EE, Farzi A, Reichmann F, Herzog H, Holzer P (2017) Visceral hyperalgesia caused by peptide YY deletion and Y2 receptor antagonism. Scientific reports 7, 40968 [PubMed:28106168] [show Abstract] Altered levels of colonic peptide YY (PYY) have been reported in patients suffering from functional and inflammatory bowel disorders. While the involvement of neuropeptide Y (NPY) and Y receptors in the regulation of nociception is well established, the physiological role of PYY in somatic and visceral pain is poorly understood. In this work, the role of PYY in pain sensitivity was evaluated using PYY knockout (PYY(-/-)) mice and Y2 receptor ligands. PYY(-/-) mice were more sensitive to somatic thermal pain compared to wild type (WT) mice. Visceral pain was assessed by evaluating pain-related behaviors, mouse grimace scale (MGS) and referred hyperalgesia after intrarectal administration of allyl isothiocyanate (AITC, 1 or 2%) or its vehicle, peanut oil. The pain-related behaviors induced by AITC were significantly exaggerated by PYY deletion, whereas the MGS readout and the referred hyperalgesia were not significantly affected. The Y2 receptor antagonist, BII0246, increased pain-related behaviors in response to intrarectal AITC compared to vehicle treatment while the Y2 receptor agonist, PYY(3-36), did not have a significant effect. These results indicate that endogenous PYY has a hypoalgesic effect on somatic thermal and visceral chemical pain. The effect on visceral pain seems to be mediated by peripheral Y2 receptors. | Zhang J, Jia H, Wang Q, Zhang Y, Wu W, Zhang H (2017) Role of Peptide YY3-36 and Glucose-Dependent Insulinotropic Polypeptide in Anorexia Induction by Trichothecences T-2 Toxin, HT-2 Toxin, Diacetoxyscirpenol, and Neosolaniol. Toxicological sciences : an official journal of the Society of Toxicology 159, 203-210 [PubMed:28666375] [show Abstract] Trichothecences, secondary metabolites produced by Fusarium, are serious health risks to humans and animals worldwide. Although type A trichothecence-induced food refusal has been observed, the mechanism underlying the anorexia caused by these compounds is not fully understood. In this study, we hypothesized that anorexia induced by type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), and neosolaniol (NEO), in mice corresponds to the changes in the gut satiety hormones peptide YY3-36 (PYY3-36) and glucose-dependent insulinotropic polypeptide (GIP) in plasma. A well-characterized mouse food refusal model was used in this assay. Oral exposure to or intraperitoneal (ip) injection of 1 mg/kg bw T-2, HT-2, DAS, or NEO resulted in dramatically decreased food intake, and PYY3-36 and GIP concentrations were elevated accordingly. Specifically, the PYY3-36 and GIP concentrations peaked at 2 h following oral exposure to these 4 toxins individually, although the durations were not identical. After ip administration of T-2 or HT-2, PYY3-36 significantly increased within 6 h. However, no significant difference was found in the DAS and NEO groups. The GIP levels peaked within 2, 2, 0.5, and 0.5 h, respectively, and remained increased up to 6, 6, 2, and 6 h, respectively, following T-2, HT-2, DAS, or NEO ip exposure. The increase in GIP was greater than that of PYY3-36 after exposure to the 4 toxins using 2 administration routes. Together, these findings suggest that PYY3-36 and GIP play a role in T-2-, HT-2-, DAS-, and NEO-induced anorexia. | Hickson M, Moss C, Dhillo WS, Bottin J, Frost G (2016) Increased peptide YY blood concentrations, not decreased acyl-ghrelin, are associated with reduced hunger and food intake in healthy older women: Preliminary evidence. Appetite 105, 320-327 [PubMed:27264721] [show Abstract] With ageing there is frequently a loss of appetite, termed anorexia of ageing, which can result in under-nutrition. We do not know how appetite control alters with ageing. The objective of this study was to investigate whether differences in the release of, and response to, gastrointestinal appetite hormones is altered in young compared to old healthy volunteers. We hypothesised that an increase in PYY and GLP-1 or a decrease ghrelin may result in a decreased appetite. A comparative experimental design, using a cross-sectional sample of ages from a healthy population, matched for sex and BMI was used. The study compared total ghrelin, acyl-ghrelin, PYY, GLP-1 and subjective appetite responses to ingestion of a standardised 2781kj (660 kcal) test meal. 31 female volunteers aged between 21 and 92yrs took part. Multiple linear regression showed that both age and sex had an independent effect on energy intake. Subjective appetite scores showed that hunger, pleasantness to eat, and prospective food intake were significantly lower in the older age groups. PYY incremental area under the curve (IAUC) was greater in the oldest old compared to younger ages f(3,27) = 2.9, p = 0.05. No differences in GLP-1, ghrelin or acyl-ghrelin were observed in the older compared to younger age groups. Our data suggest that there may be increases in postprandial PYY(3-36) levels in female octogenarians, potentially resulting in reduced appetite. There does not appear to be any change in ghrelin or acyl-ghrelin concentrations with ageing. | Henry KE, Kerwood DJ, Allis DG, Workinger JL, Bonaccorso RL, Holz GG, Roth CL, Zubieta J, Doyle RP (2016) Solution Structure and Constrained Molecular Dynamics Study of Vitamin B12 Conjugates of the Anorectic Peptide PYY(3-36). ChemMedChem 11, 1015-1021 [PubMed:27027248] [show Abstract] Vitamin B12 -peptide conjugates have considerable therapeutic potential through improved pharmacokinetic and/or pharmacodynamic properties imparted on the peptide upon covalent attachment to vitamin B12 (B12 ). There remains a lack of structural studies investigating the effects of B12 conjugation on peptide secondary structure. Determining the solution structure of a B12 -peptide conjugate or conjugates and measuring functions of the conjugate(s) at the target peptide receptor may offer considerable insight concerning the future design of fully optimized conjugates. This methodology is especially useful in tandem with constrained molecular dynamics (MD) studies, such that predictions may be made about conjugates not yet synthesized. Focusing on two B12 conjugates of the anorectic peptide PYY(3-36), one of which was previously demonstrated to have improved food intake reduction compared with PYY(3-36), we performed NMR structural analyses and used the information to conduct MD simulations. The study provides rare structural insight into vitamin B12 conjugates and validates the fact that B12 can be conjugated to a peptide without markedly affecting peptide secondary structure. | Kuehl PJ, Boyden T, Dobry DE, Doyle-Eisele M, Friesen DT, McDonald JD, Murri BG, Vodak DT, Lyon DK (2016) Inhaled PYY(3-36) dry-powder formulation for appetite suppression. Drug development and industrial pharmacy 42, 150-156 [PubMed:26006332] [show Abstract]
ObjectivePeptide YY3-36 [PYY(3-36)] has shown efficacy in appetite suppression when dosed by injection modalities (intraperitoneal (IP)/subcutaneous). Transitioning to needle-free delivery, towards inhalation, often utilizes systemic pharmacokinetics as a key endpoint to compare different delivery methods and doses. Systemic pharmacokinetics were evaluated for PYY3-36 when delivered by IP, subcutaneous, and inhalation, the systemic pharmacokinetics were then used to select doses in an appetite suppression pharmacodynamic study.MethodsDry-powder formulations were manufactured by spray drying and delivered to mice via nose only inhalation. The systemic plasma, lung tissue, and bronchoalveolar lavage fluid pharmacokinetics of different inhalation doses of PYY(3-36) were compared to IP and subcutaneous efficacious doses. Based on these pharmacokinetic data, inhalation doses of 70:30 PYY(3-36):Dextran T10 were evaluated in a mouse model of appetite suppression and compared to IP and subcutaneous data.ResultsInhalation pharmacokinetic studies showed that plasma exposure was similar for a 2 × higher inhalation dose when compared to subcutaneous and IP delivery. Inhalation doses of 0.22 and 0.65 mg/kg were for efficacy studies. The results showed a dose-dependent (not dose proportional) decrease in food consumption over 4 h, which is similar to IP and subcutaneous delivery routes.ConclusionsThe pharmacokinetic and pharmacodynamics results substantiate the ability of pharmacokinetic data to inform pharmacodynamics dose selection for inhalation delivery of the peptide PYY(3-36). Additionally, engineered PYY(3-36):Dextran T10 particles delivered to the respiratory tract show promise as a non-invasive therapeutic for appetite suppression. | Gonzalez R, Unniappan S (2016) Mass spectrometry-assisted confirmation of the inability of dipeptidyl peptidase-4 to cleave goldfish peptide YY(1-36) and the lack of anorexigenic effects of peptide YY(3-36) in goldfish (Carassius auratus). Fish physiology and biochemistry 42, 831-844 [PubMed:26676513] [show Abstract] Dipeptidyl peptidase-4 (DPP4) is a serine protease of great interest because it has been shown to modulate the activity of several peptidergic factors including peptide YY (PYY) and glucagon-like peptide-1/2. While PYY(1-36) is orexigenic in mammals, PYY(3-36) recently garnered interest as a potent anorexigen. In silico phylogenetic analysis found that the DPP4 cleavage sites are absent in fish PYY sequences. However, no studies were conducted to show that indeed PYY(3-36) is not produced by DPP4 in fish. If DPP4 does not cleave PYY(1-36), is PYY(3-36) an anorexigen in fish? The objectives of this research were to (1) test whether DPP4 cleaves goldfish PYY(1-36) and (2) determine whether PYY(3-36) is an anorexigen in goldfish. First, we identified the highly conserved catalytic region of DPP4 in goldfish. Abundant expression of DPP4 mRNA was found within the gastrointestinal tract. We also report the first MALDI-MS cleavage analysis of DPP4 effects on PYY(1-36) in a non-mammalian vertebrate. Our novel results indicate that DPP4 is unable to cleave goldfish PYY(1-36) to PYY(3-36) in vitro. It also confirms a previously held hypothesis that DPP4 is unable to cleave fish PYY(1-36) that contains N-terminal proline-proline residues. PYY(3-36) had no effects on food intake of goldfish. The appetite inhibitory effects of intraperitoneal and intracerebroventricular injections of 10 ng/g body weight gfPYY(1-36) were abolished by coinjections of BIBP3226, a Y1 receptor antagonist. These results are significant because it shows the lack of generation of endogenous PYY(3-36) and its anorectic effects in goldfish. | Svane MS, Jørgensen NB, Bojsen-Møller KN, Dirksen C, Nielsen S, Kristiansen VB, Toräng S, Wewer Albrechtsen NJ, Rehfeld JF, Hartmann B, Madsbad S, Holst JJ (2016) Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery. International journal of obesity (2005) 40, 1699-1706 [PubMed:27434221] [show Abstract]
Background/objectivesExaggerated postprandial secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) may explain appetite reduction and weight loss after Roux-en-Y gastric bypass (RYGB), but causality has not been established. We hypothesized that food intake decreases after surgery through combined actions from GLP-1 and PYY. GLP-1 actions can be blocked using the GLP-1 receptor antagonist Exendin 9-39 (Ex-9), whereas PYY actions can be inhibited by the administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor preventing the formation of PYY3-36.Subjects/methodsAppetite-regulating gut hormones and appetite ratings during a standard mixed-meal test and effects on subsequent ad libitum food intake were evaluated in two studies: in study 1, nine patients with type 2 diabetes were examined prospectively before and 3 months after RYGB with and without Ex-9. In study 2, 12 RYGB-operated patients were examined in a randomized, placebo-controlled, crossover design on four experimental days with: (1) placebo, (2) Ex-9, (3) the DPP-4 inhibitor, sitagliptin, to reduce formation of PYY3-36 and (4) Ex-9/sitagliptin combined.ResultsIn study 1, food intake decreased by 35% following RYGB compared with before surgery. Before surgery, GLP-1 receptor blockage increased food intake but no effect was seen postoperatively, whereas PYY secretion was markedly increased. In study 2, combined GLP-1 receptor blockage and DPP-4 inhibitor mediated lowering of PYY3-36 increased food intake by ~20% in RYGB patients, whereas neither GLP-1 receptor blockage nor DPP-4 inhibition alone affected food intake, perhaps because of concomitant marked increases in the unblocked hormone.ConclusionsBlockade of actions from only one of the two L-cell hormones, GLP-1 and PYY3-36, resulted in concomitant increased secretion of the other, probably explaining the absent effect on food intake on these experimental days. Combined blockade of GLP-1 and PYY actions increased food intake after RYGB, supporting that these hormones have a role in decreased food intake postoperatively. | Khan D, Vasu S, Moffett RC, Irwin N, Flatt PR (2016) Islet distribution of Peptide YY and its regulatory role in primary mouse islets and immortalised rodent and human beta-cell function and survival. Molecular and cellular endocrinology 436, 102-113 [PubMed:27465830] [show Abstract] Recent evidence suggests that the classic gut peptide, Peptide YY (PYY), could play a fundamental role in endocrine pancreatic function. In the present study expression of PYY and its NPY receptors on mouse islets and immortalised rodent and human beta-cells was examined together with the effects of both major circulating forms of PYY, namely PYY(1-36) and PYY(3-36), on beta-cell function, murine islet adaptions to insulin deficiency/resistance, as well as direct effects on cultured beta-cell proliferation and apoptosis. In vivo administration of PYY(3-36), but not PYY(1-36), markedly (p < 0.05) decreased food intake in overnight fasted mice. Neither form of PYY affected glucose disposal or insulin secretion following an i.p. glucose challenge. However, in vitro, PYY(1-36) and PYY(3-36) inhibited (p < 0.05 to p < 0.001) glucose, alanine and GLP-1 stimulated insulin secretion from immortalised rodent and human beta-cells, as well as isolated mouse islets, by impeding alterations in membrane potential, [Ca(2+)]i and elevations of cAMP. Mice treated with multiple low dose streptozotocin presented with severe (p < 0.01) loss of beta-cell mass accompanied by notable increases (p < 0.001) in alpha and PP cell numbers. In contrast, hydrocortisone-induced insulin resistance increased islet number (p < 0.01) and beta-cell mass (p < 0.001). PYY expression was consistently observed in alpha-, PP- and delta-, but not beta-cells. Streptozotocin decreased islet PYY co-localisation with PP (p < 0.05) and somatostatin (p < 0.001), whilst hydrocortisone increased PYY co-localisation with glucagon (p < 0.05) in mice. More detailed in vitro investigations revealed that both forms of PYY augmented (p < 0.05 to p < 0.01) immortalised human and rodent beta-cell proliferation and protected against streptozotocin-induced cytotoxicity, to a similar or superior extent as the well characterised beta-cell proliferative and anti-apoptotic agent GLP-1. Taken together, these data highlight the significance and potential offered by modulation of pancreatic islet NPY receptor signalling pathways for preservation of beta-cell mass in diabetes. | Olsen J, Kofoed J, Østergaard S, Wulff BS, Nielsen FS, Jorgensen R (2016) Metabolism of peptide YY 3-36 in Göttingen mini-pig and rhesus monkey. Peptides 78, 59-67 [PubMed:26774588] [show Abstract] Peptide YY 3-36-amide (PYY3-36) is a peptide hormone, which is known to decrease appetite and food-intake by activation of the Y2 receptor. The current studies were designed to identify the metabolites of PYY3-36 in mini-pig and rhesus monkey. Plasma samples were analyzed by high resolution LC-MS (and MS/MS) in order to unambiguously identify the metabolites of PYY3-36. In summary, the metabolism of PYY3-36 was similar in mini-pig and rhesus monkey. Several metabolites were identified and PYY3-34 was identified at the highest levels in plasma. In addition, mini-pigs were also dosed with PYY1-36-amide, PYY3-35, PYY3-34 and [N-methyl 34Q]-PYY3-36-amide in order to investigate the mechanisms by which PYY was metabolized. PYY3-35 was rapidly converted to PYY3-34 whereas dosing of PYY3-34 to mini-pigs only showed circulating degradation products at low levels, i.e., PYY3-34 was metabolically more stable than PYY3-36 and PYY3-35. [N-methyl 34Q]-PYY3-36-amide was hypothesized to be stable toward cleavage between 34Q and 35R and after i.v. administration to mini-pigs, one major cleavage product was identified as [N-methyl 34Q]-PYY3-35. Overall, this showed that cleavage between 35R and 36Y was possible as well as between 34Q and 35R (as shown for PYY3-35), which indicated that metabolism of PYY3-36 to PYY3-34 may be a two-step process. PYY1-36 was also dosed to mini-pigs, which showed that PYY1-36 was metabolized in the C-terminal as PYY3-36. The overall degradation pattern of PYY1-36 was more complex due to the simultaneous enzymatic degradation in the N-terminal to form PYY2-34/36 and PYY3-34/36. In vitro incubations with heparin stabilized plasma showed that PYY3-36 was degraded with a half-life of 175 min, whereas incubations with PYY3-35 (half-life of 6 min) showed a rapid formation of PYY3-34. In conclusion, the present studies showed that PYY3-36 underwent enzymatic degradation in the C-terminal part and that the major circulating metabolite was PYY3-34. Furthermore, it may be a sequential two-step process leading to the formation of PYY3-35 and subsequently the metabolically more stable PYY3-34. | Reidelberger R, Haver A, Anders K, Apenteng B, Lanio C (2016) Effects of solid-phase extraction of plasma in measuring gut metabolic hormones in fasted and fed blood of lean and diet-induced obese rats. Physiological reports 4, e12800 [PubMed:27207785] [show Abstract] Glucagon-like peptide-1 (GLP-1), peptide YY (3-36) [PYY(3-36)], amylin, ghrelin, insulin, and leptin are thought to act as hormonal signals from periphery to brain to control food intake. Here, we determined the effects of solid-phase extraction of plasma in measuring these hormones in blood of lean and diet-induced obese rats. Individual enzyme-linked immunoassays and a multiplex assay were used to measure active GLP-1, total PYY, active amylin, active ghrelin, insulin, leptin, and total GIP in response to (1) addition of known amounts of the peptides to lean and obese plasma, (2) a large meal in lean and obese rats, and (3) intravenous infusions of anorexigenic doses of GLP-1, PYY(3-36), amylin, and leptin in lean rats. Extraction of lean and obese plasma prior to assays produced consistent recoveries across assays for GLP-1, PYY, amylin, ghrelin, and insulin, reflecting losses inherent to the extraction procedure. Plasma extraction prior to assays generally revealed larger meal-induced changes in plasma GLP-1, PYY, amylin, ghrelin, and insulin in lean and obese rats. Plasma extraction and the multiplex assay were used to compare plasma levels of GLP-1, PYY, and amylin after a large meal with plasma levels produced by IV infusions of anorexigenic doses of GLP-1, PYY(3-36), and amylin. Infusions produced dose-dependent increases in plasma peptide levels, which were well above their postprandial levels. These results do not support the hypothesis that postprandial plasma levels of GLP-1, PYY(3-36), and amylin are sufficient to decrease food intake by an endocrine mechanism. | Schmidt JB, Sjödin A, Stevner LS, Ritz C, Michaelsen NB, Thomsen AB, Holst JJ, Astrup A (2016) Serum lipase activity and concentration during intravenous infusions of GLP-1 and PYY3-36 and after ad libitum meal ingestion in overweight men. Physiological reports 4, e12980 [PubMed:27670407] [show Abstract] To examine the effect on serum lipase activity and protein concentration of intravenous infusions of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY3-36) and of an ad libitum meal in healthy overweight men. Twenty-five healthy, male subjects participated in this randomized, double-blinded, placebo-controlled 4-arm crossover study (Body Mass Index (BMI): 29 ± 3 kg/m2, age: 33 ± 9 years). On separate days, the subjects received a 150-min intravenous infusion of either (1) 0.8 pmol/kg/min PYY3-36, (2) 1.0 pmol/kg/min GLP-1, (3) 1 + 2, or (4) placebo. Samples were collected throughout the infusion and after intake of an ad libitum meal for measurement of serum lipase. Serum lipase levels measured by enzyme-linked immunosorbent assay (ELISA) following mono-infusions of GLP-1 and PYY3-36 were comparable to serum lipase levels following placebo (P = 0.054 and P = 0.873, respectively). Following the co-infusion of GLP-1 and PYY3-36, serum lipase levels measured by ELISA decreased over time compared to placebo (P = 0.012). However, the between-group difference was not consistent when each time point was analyzed separately. On the placebo day, serum lipase levels measured by ELISA after an ad libitum meal rose slightly compared to the preprandial values (P = 0.003). There was strong correlation between serum lipase levels measured by ELISA and LIPC Lipase colorimetric assay (COBAS) (0.94 < r; <0.0001). Infusions of GLP-1 and PYY3-36, separately or in combination, did not increase serum lipase. However, a small increase in serum lipase may occur in response to a meal. | Alhadeff AL, Golub D, Hayes MR, Grill HJ (2015) Peptide YY signaling in the lateral parabrachial nucleus increases food intake through the Y1 receptor. American journal of physiology. Endocrinology and metabolism 309, E759-66 [PubMed:26330345] [show Abstract] Although central PYY delivery potently increases food intake, the sites of action and mechanisms mediating these hyperphagic effects are not fully understood. The present studies investigate the contribution of lateral parabrachial nucleus (lPBN) PYY-Y receptor signaling to food intake control, as lPBN neurons express Y receptors and receive PYY fibers and are known to integrate circulating and visceral sensory signals to regulate energy balance. Immunohistochemical results identified a subpopulation of gigantocellular reticular nucleus PYY-producing neurons that project monosynaptically to the lPBN, providing an endogenous source of PYY to the lPBN. lPBN microinjection of PYY-(1-36) or PYY-(3-36) markedly increased food intake by increasing meal size. To determine which receptors mediate these behavioral results, we first performed quantitative real-time PCR to examine the relative levels of Y receptor expression in lPBN tissue. Gene expression analyses revealed that, while Y1, Y2, and Y5 receptors are each expressed in lPBN tissue, Y1 receptor mRNA is expressed at fivefold higher levels than the others. Furthermore, behavioral/pharmacological results demonstrated that the hyperphagic effects of PYY-(3-36) were eliminated by lPBN pretreatment with a selective Y1 receptor antagonist. Together, these results highlight the lPBN as a novel site of action for the intake-stimulatory effects of central PYY-Y1 receptor signaling. | Siahanidou T, Margeli A, Tsirogianni C, Hantzi E, Papassotiriou I, Chrousos G (2015) Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates with infection. Clinical chemistry and laboratory medicine 53, 1815-1824 [PubMed:25870965] [show Abstract]
BackgroundEarly diagnosis and treatment of neonatal infection is important to prevent morbidity and mortality. The gastrointestinal tract-derived hormones ghrelin and peptide YY (PYY), which participate in the regulation of food intake and energy balance, may also play roles in the inflammatory response. Their involvement in neonatal infection is not known.MethodsPlasma ghrelin and PYY(3-36) levels were serially measured (by ELISA) on Days 0, 1, 2, 3 and 7 following admission in 36-term neonates with febrile infection (22 of them were septic) and once in 20 healthy term neonates of similar postnatal age and gender distribution, as controls. Associations of ghrelin and PYY(3-36) levels with clinical and laboratory parameters, including anthropometrics, fever, leukocyte and platelet counts, serum glucose, C-reactive protein (CRP) and serum amyloid A levels, were assessed.ResultsPlasma ghrelin levels were significantly higher in infected neonates than in controls at each study day (p=0.009), whereas PYY(3-36) levels did not differ significantly between patients and controls at any day. In infected neonates, ghrelin levels on admission correlated negatively with serum glucose levels (p=0.003), whereas fever change during the course of infection was significantly associated with change of ghrelin levels (p=0.01). Receiver operating characteristic analysis of ghrelin levels resulted in significant areas under the curve (AUC) for detecting infected neonates on admission (AUC=0.728, p=0.005).ConclusionsCirculating ghrelin, but not PYY(3-36), levels are increased in neonates with infection, possibly reflecting and/or participating in the inflammatory process. | Henry KE, Elfers CT, Burke RM, Chepurny OG, Holz GG, Blevins JE, Roth CL, Doyle RP (2015) Vitamin B12 conjugation of peptide-YY(3-36) decreases food intake compared to native peptide-YY(3-36) upon subcutaneous administration in male rats. Endocrinology 156, 1739-1749 [PubMed:25658456] [show Abstract] Challenges to peptide-based therapies include rapid clearance, ready degradation by hydrolysis/proteolysis, and poor intestinal uptake and/or a need for blood brain barrier transport. This work evaluates the efficacy of conjugation of vitamin B12 (B12) on sc administered peptide tyrosine tyrosine (PYY)(3-36) function. In the current experiments, a B12-PYY(3-36) conjugate was tested against native PYY(3-36), and an inactive conjugate B12-PYYC36 (null control) in vitro and in vivo. In vitro experiments demonstrated similar agonism for the neuropeptide Y2 receptor by the B12-PYY(3-36) conjugate (EC50 26.5 nM) compared with native PYY(3-36) (EC50 16.0 nM), with the null control having an EC50 of 1.8 μM. In vivo experiments were performed in young adult male Sprague Dawley rats (9 wk). Daily treatments were delivered sc in five 1-hour pulses, each pulse delivering 5-10 nmol/kg, by implanted microinfusion pumps. Increases in hindbrain Fos expression were comparable 90 minutes after B12-PYY(3-36) or PYY3-36 injection relative to saline or B12-PYYC36. Food intake was reduced during a 5-day treatment for both B12-PYY(3-36)- (24%, P = .001) and PYY(3-36)-(13%, P = .008) treated groups relative to baseline. In addition, reduction of food intake after the three dark cycle treatment pulses was more consistent with B12-PYY(3-36) treatment (-26%, -29%, -27%) compared with the PYY(3-36) treatment (-3%, -21%, -16%), and B12-PYY(3-36) generated a significantly longer inhibition of food intake vs. PYY(3-36) treatment after the first two pulses (P = .041 and P = .036, respectively). These findings demonstrate a stronger, more consistent, and longer inhibition of food intake after the pulses of B12-PYY(3-36) conjugate compared with the native PYY(3-36). | Stadlbauer U, Woods SC, Langhans W, Meyer U (2015) PYY3-36: Beyond food intake. Frontiers in neuroendocrinology 38, 1-11 [PubMed:25527432] [show Abstract] The gastrointestinal hormone peptide tyrosine tyrosine 3-36 (PYY(3-36)) has attained broad recognition with respect to its involvement in energy homeostasis and the control of food intake. It is mainly secreted by distal intestinal enteroendocrine L-cells in response to eating and exerts neurally mediated, paracrine and endocrine effects on various target organs. In addition to its gastrointestinal effects, PYY(3-36) has long been known to inhibit food intake. Recent closer examination of the effects of PYY(3-36) revealed that this gut-derived peptide also influences a wide spectrum of behavioral and cognitive functions that are pivotal for basic processes of perception and judgment, including central information processing, salience learning, working memory, and behavioral responding to novelty. Here, we review the effects of PYY(3-36) that go beyond food intake and provide a conceptual framework suggesting that several apparently unrelated behavioral actions of PYY(3-36) may actually reflect different manifestations of modulating the central dopamine system. | Eddy KT, Lawson EA, Meade C, Meenaghan E, Horton SE, Misra M, Klibanski A, Miller KK (2015) Appetite regulatory hormones in women with anorexia nervosa: binge-eating/purging versus restricting type. The Journal of clinical psychiatry 76, 19-24 [PubMed:25098834] [show Abstract]
ObjectiveAnorexia nervosa is a psychiatric illness characterized by low weight, disordered eating, and hallmark neuroendocrine dysfunction. Behavioral phenotypes are defined by predominant restriction or bingeing/purging; binge-eating/purging type anorexia nervosa is associated with poorer outcome. The pathophysiology underlying anorexia nervosa types is unknown, but altered hormones, known to be involved in eating behaviors, may play a role.MethodTo examine the role of anorexigenic hormones in anorexia nervosa subtypes, we examined serum levels of peptide YY (PYY; total and active [3-36] forms), brain-derived neurotrophic factor (BDNF), and leptin as primary outcomes in women with DSM-5 restricting type anorexia nervosa (n = 50), binge-eating/purging type anorexia nervosa (n = 25), and healthy controls (n = 22). In addition, women completed validated secondary outcome measures of eating disorder psychopathology (Eating Disorder Examination-Questionnaire) and depression and anxiety symptoms (Hamilton Rating Scales for Depression [HDRS] and Anxiety [HARS]). The study samples were collected from May 22, 2004, to February 7, 2012.ResultsMean PYY 3-36 and leptin levels were lower and BDNF levels higher in binge-eating/purging type anorexia nervosa than in restricting type anorexia nervosa (all P values < .05). After controlling for body mass index, differences in PYY and PYY 3-36 between anorexia nervosa types were significant (P < .05) and differences in BDNF were at the trend level (P < .10). PYY 3-36 was positively (r = 0.27, P = .02) and leptin was negatively (r = -0.51, P < .0001) associated with dietary restraint; BDNF was positively associated with frequency of purging (r = 0.21, P = .04); and leptin was negatively associated with frequency of bingeing (r = -0.29, P = .007) and purging (r = -0.31, P = .004).ConclusionsAmong women with anorexia nervosa, the anorexigenic hormones PYY, BDNF, and leptin are differentially regulated between the restricting and binge/purge types. Whether these hormone pathways play etiologic roles with regard to anorexia nervosa behavioral types or are compensatory merits further study. | Prado WL, Balagopal PB, Lofrano-Prado MC, Oyama LM, Tenório TR, Botero JP, Hill JO (2014) Effect of aerobic exercise on hunger feelings and satiety regulating hormones in obese teenage girls. Pediatric exercise science 26, 463-469 [PubMed:25372381] [show Abstract] Exercise is implicated in modifying subsequent energy intake (EI) through alterations in hunger and/or satiety hormones. Our aim was to examine the effects of aerobic exercise on hunger, satiety regulatory peptides, and EI in obese adolescents. Nine obese girls (age: 13-18 years old, BMI: 33.74 ± 4.04 kg/m2) participated in this randomized controlled crossover study. Each participant randomly underwent 2 experimental protocols: control (seated for 150 min) and exercise (exercised for 30 min on a treadmill performed at ventilatory threshold [VT] intensity and then remained seated for 120 min). Leptin, peptide YY(3-36) (PYY(3-36)), and subjective hunger were measured at baseline as well as 30 min and 150 min, followed by 24-hr EI measurement. Exercise session resulted in an acute increase in PYY(3-36) (p < .01) without changes in leptin and/or hunger scores. The control session increased hunger scores (p < .01) and decreased circulating leptin levels (p = .03). There was a strong effect size for carbohydrate intake (d = 2.14) and a modest effect size for protein intake (d = 0.61) after the exercise compared with the control session. Exercise performed at VT intensity in this study appears to provoke a state of transient anorexia in obese girls. These changes may be linked to an increase in circulating PYY3-36 and maintenance of leptin levels. |
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