RPEP-00074 · 1988The mu-selective opioid agonist DAGO (Tyr-D-Ala-Gly-(Me)Phe-Gly-ol) increased food intake when injected into the central nucleus of the amygdala at doses of 1 and 3 nanomoles.
Neither DSLET (a delta-selective agonist) nor dynorphin A (a kappa-selective agonist) affected food intake at the same location, even at the highest dose of 3 nanomoles.
Dynorphin A did increase food intake when injected into the medial hypothalamus at 2 nanomoles. This shows that different brain regions use different opioid receptor types to control eating.
Bilateral injections of DAGO were no more effective than unilateral injections. Naloxone and the long-acting antagonist beta-chlornaltrexamine both blocked DAGO's feeding effect, confirming opioid receptor involvement.
Gosnell, B A · Animal Study
RPEP-00196 · 1991Pancreatic polypeptides and dynorphin A stimulated feeding in satiated dogs. NPY, galanin, norepinephrine, and GRH did not, despite working in rats.
Inui, A; Okita, M; Nakajima, M; Inoue, T; Sakatani, N; Oya, M; Morioka, H; Okimura, Y; Chihara, K; Baba, S · Animal Study
RPEP-00208 · 1991Dexfenfluramine's anorectic effect dominated over opioid agonist feeding stimulation. The interaction was not mediated by brain serotonin turnover changes.
Robert, J J; Orosco, M; Rouch, C; Cohen, Y; Jacquot, C · Animal Study
RPEP-00274 · 1993Weight-loss-promoting phenylpiperidine antagonists like LY255582 had high affinity for the kappa-2B binding site. Non-weight-loss compounds did not.
Rothman, R B; Xu, H; Char, G U; Kim, A; De Costa, B R; Rice, K C; Zimmerman, D M · Animal Study
RPEP-00301 · 1994A highly palatable meal significantly increased post-meal beta-endorphin, pancreatic polypeptide, and neurotensin compared to the same unpalatable meal.
Melchior, J C; Rigaud, D; Chayvialle, J A; Colas-Linhart, N; Laforest, M D; Petiet, A; Comoy, E; Apfelbaum, M · Cross Sectional
RPEP-00315 · 1995The human Y4 receptor was cloned and shown to bind pancreatic polypeptide, NPY, and PYY, expanding the known receptor family for these appetite-regulating peptides.
Bard, J A; Walker, M W; Branchek, T A; Weinshank, R L · In Vitro
RPEP-00321 · 1995The human Y2 receptor was cloned from hippocampus and shown to selectively bind NPY and PYY but not pancreatic polypeptide.
Gerald, C; Walker, M W; Vaysse, P J; He, C; Branchek, T A; Weinshank, R L · In Vitro
RPEP-00394 · 1996Ad libitum access to a high-fat/sucrose diet significantly increased hypothalamic dynorphin peptide and mRNA levels compared to standard diet, suggesting opioid peptide-mediated overeating.
Welch, C C; Kim, E M; Grace, M K; Billington, C J; Levine, A S · Animal Study
RPEP-00497 · 1998MK-677 (25 mg/day for 8 weeks) increased 24-hour GH secretion rate by 1.8-fold, normalized pulsatile GH profiles, increased fat-free mass by ~3 kg, and raised basal metabolic rate in obese males.
Svensson, J; Lönn, L; Jansson, J O; Murphy, G; Wyss, D; Krupa, D; Cerchio, K; Polvino, W; Gertz, B; Boseaus, I; Sjöström, L; Bengtsson, B A · RCT
RPEP-00564 · 1999MK-677 increased serum leptin levels independent of body fat changes, increased testosterone, and had no effect on thyroid hormones in obese males, revealing metabolic effects dissociated from fat mass changes.
Svensson, J; Carlsson, B; Carlsson, L M; Jansson, J O; Bengtsson, B A · RCT
RPEP-00583 · 2000Food intake regulation involves convergent afferent signals from gut peptides (CCK, GLP-1, PYY, ghrelin), adipose tissue (leptin), vagal mechanoreceptors, and higher brain centers, all integrated by hypothalamic circuitry.
Bray, G A · Review
RPEP-00598 · 2000Obese Zucker rats had reduced arcuate POMC mRNA and PVN alpha-MSH levels compared to lean controls, indicating impaired melanocortin satiety signaling as a driver of genetic obesity.
Kim, E M; O'Hare, E; Grace, M K; Welch, C C; Billington, C J; Levine, A S · Animal Study
RPEP-00608 · 2000Oral AOD9604 — a synthetic peptide fragment based on the fat-burning region of human growth hormone — reduced weight gain by over 50% in obese Zucker rats. Treated animals gained only 15.8 g versus 35.6 g in controls over 19 days of daily oral dosing at 500 µg/kg body weight. Fat tissue from treated animals showed increased lipolytic (fat-breaking) activity.
Critically, unlike full-length growth hormone (which is known to worsen insulin resistance with chronic use), AOD9604 showed no adverse effects on insulin sensitivity when tested with euglycemic clamp techniques — considered the gold standard for measuring insulin action. This separation of fat-burning benefits from growth hormone's diabetogenic side effects was the key finding.
Ng, F M; Sun, J; Sharma, L; Libinaka, R; Jiang, W J; Gianello, R · Animal Study
RPEP-00612 · 2000Hybrid CCK-A agonist peptides combining structural features of hexapeptide and tetrapeptide classes showed potent receptor binding and selectivity, advancing design of satiety-inducing peptide drugs for obesity.
Pierson, M E; Comstock, J M; Simmons, R D; Julien, R; Kaiser, F; Rosamond, J D · In Vitro
RPEP-00645 · 2001Ghrelin stimulated food intake and weight gain in rats through vagal and hypothalamic mechanisms, with ghrelin levels suppressed by feeding and increased by leptin, establishing the ghrelin-leptin axis for appetite regulation.
Asakawa, A; Inui, A; Kaga, T; Yuzuriha, H; Nagata, T; Ueno, N; Makino, S; Fujimiya, M; Niijima, A; Fujino, M A; Kasuga, M · Animal Study
RPEP-00649 · 2001CPE-fat mice showed impaired prohormone convertase activity resulting in defective processing of opioid peptides (prodynorphin, proenkephalin) and other peptide hormones, linking peptide processing dysfunction to obesity.
Berman, Y; Mzhavia, N; Polonskaia, A; Devi, L A · Animal Study
RPEP-00668 · 2001Appetite regulation involves two integrated time scales: acute meal-by-meal gut peptide signals (CCK, GLP-1, ghrelin, PYY) and chronic body weight signals (leptin, insulin), converging on hypothalamic and brainstem integration centers.
Havel, P J · Review
RPEP-00687 · 2001Gut peptides (ghrelin, CCK, GLP-1, PYY) regulate appetite through neural and hormonal pathways that are significantly disrupted by gastrointestinal surgery, requiring surgical awareness for optimal patient management.
Näslund, E; Hellström, P M; Kral, J G · Review
RPEP-00705 · 2001IV ghrelin infusion in healthy humans increased subjective appetite ratings and food intake significantly, alongside GH stimulation, providing the first proof that ghrelin is a human hunger hormone.
Wren, A M; Seal, L J; Cohen, M A; Brynes, A E; Frost, G S; Murphy, K G; Dhillo, W S; Ghatei, M A; Bloom, S R · RCT
RPEP-00711 · 2002The ghrelin-GHS system is a multi-functional endocrine network with validated roles in GH regulation, appetite control, adiposity, and cardiovascular function, with therapeutic implications across multiple medical specialties.
Arvat, Emanuela; Broglio, Fabio; Aimaretti, Gianluca; Benso, Andrea; Giordano, Roberta; Deghenghi, Romano; Ghigo, Ezio · Review
RPEP-00717 · 2002Ghrelin displays endocrine (GH release) and non-endocrine (appetite stimulation, adipogenesis, cardioprotection) activities, with cardiovascular protection mediated by both acyl and des-acyl forms — a multi-system metabolic hormone.
Broglio, Fabio; Arvat, Emanuela; Benso, Andrea; Papotti, Mauro; Muccioli, Giampiero; Deghenghi, Romano; Ghigo, Ezio · Review
RPEP-00718 · 2002Ghrelin acts as a multi-system metabolic regulator beyond GH release, with validated roles in appetite, energy balance, gastric motility, pancreatic function, cardiovascular regulation, and immune modulation through widely distributed receptors.
Broglio, Fabio; Arvat, Emanuela; Benso, Andrea; Gottero, Cristina; Prodam, Flavia; Granata, Riccarda; Papotti, Mauro; Muccioli, Giampiero; Deghenghi, Romano; Ghigo, Ezio · Review
RPEP-00734 · 2002The arcuate nucleus integrates peripheral metabolic signals through distinct neuronal populations: ghrelin mimetic activated neurons separate from those responding to leptin and insulin, which showed overlapping activation patterns.
Hewson, Adrian K; Tung, Loraine Y C; Connell, David W; Tookman, Laura; Dickson, Suzanne L · Animal Study
RPEP-00741 · 2002Ghrelin is the only known circulating orexigenic hormone, with meal-related fluctuations and interactions with leptin, insulin, and hypothalamic neuropeptides integrating peripheral and central appetite regulation.
Kojima, Masayasu; Kangawa, Kenji · Review
RPEP-00753 · 2002Ghrelin's peripheral metabolic actions — orexigenic signaling, adipogenic activity, and cardiovascular protection — establish it as a master metabolic coordinator with therapeutic targets for obesity, cachexia, and cardiovascular disease.
Muccioli, Giampiero; Tschöp, Matthias; Papotti, Mauro; Deghenghi, Romano; Heiman, Mark; Ghigo, Ezio · Review
RPEP-00759 · 2002Dietary peptides from protein digestion induced satiety through both CCK-A and peripheral opioid receptor pathways, with the relative contribution of each pathway varying by protein source — different foods activate different satiety signals.
Pupovac, Jelena; Anderson, G Harvey · Animal Study
RPEP-00765 · 2002Intracerebroventricular chicken ghrelin and GHRP-2 inhibited food intake in neonatal chicks — the opposite of the appetite-stimulating effect in mammals — revealing a fundamental species difference in ghrelin signaling.
Saito, Ei-suke; Kaiya, Hiroyuki; Takagi, Tomo; Yamasaki, Izumi; Denbow, D Michael; Kangawa, Kenji; Furuse, Mitsuhiro · Animal Study
RPEP-00770 · 2002Hypothalamic GHS-R antisense knockdown reduced both GH secretion and body weight/food intake in rats, confirming the hypothalamic receptor's dual role in mediating GH release and appetite regulation by ghrelin/GHS.
Shuto, Yujin; Shibasaki, Tamotsu; Otagiri, Asuka; Kuriyama, Hideki; Ohata, Hisayuki; Tamura, Hideki; Kamegai, Jun; Sugihara, Hitoshi; Oikawa, Shinichi; Wakabayashi, Ichiji · Animal Study
RPEP-00779 · 2002GHRP-2 increased fat mass in NPY knockout mice, demonstrating that GH secretagogue-induced adiposity is mediated by hypothalamic AgRP rather than NPY, identifying a critical alternative pathway for ghrelin's metabolic effects.
Tschöp, Matthias; Statnick, Michael A; Suter, Todd M; Heiman, Mark L · Animal Study
RPEP-00780 · 2002Ghrelin-induced adiposity required intact pituitary function (eliminated by hypophysectomy), while gastric ghrelin secretion paradoxically increased after pituitary removal — revealing pituitary-to-stomach feedback regulation of ghrelin.
Tschöp, Matthias; Flora, David B; Mayer, John P; Heiman, Mark L · Animal Study
RPEP-00804 · 2003Peripheral PYY3-36 acutely suppressed food intake and altered hypothalamic neuropeptide expression (decreased NPY, increased POMC) in mice, confirming it as a gut-derived satiety signal that modulates central appetite gene programs.
Challis, B G; Pinnock, S B; Coll, A P; Carter, R N; Dickson, S L; O'Rahilly, S · Animal Study
RPEP-00807 · 2003Gastric pacing in morbidly obese patients altered circulating CCK, somatostatin, and leptin levels, providing a neuroendocrine mechanism for the satiety and weight loss effects of this device.
Cigaina, Valerio; Hirschberg, Angelica L · Clinical Trial
RPEP-00813 · 2003Satiety is controlled by a two-tier peripheral signaling system: short-term gut peptides (CCK, GLP-1, PYY, ghrelin, oxyntomodulin) for meal control and long-term adiposity signals (leptin, insulin) for body weight regulation, integrated by brainstem and hypothalamic circuits.
Drazen, Deborah L; Woods, Stephen C · Review
RPEP-00822 · 2003Whey protein produced greater short-term satiety than casein in humans, with faster amino acid absorption, higher plasma amino acid peaks, and different gastrointestinal hormone (CCK, GLP-1) profiles.
Hall, W L; Millward, D J; Long, S J; Morgan, L M · Clinical Trial
RPEP-00828 · 2003Ghrelin's unique status as the only circulating appetite-promoting hormone, combined with evidence from knockout and antibody studies, makes it a rational anti-obesity drug target for reducing hunger and fat accumulation.
Horvath, Tamas L; Castañeda, Tamara; Tang-Christensen, Mads; Pagotto, Uberto; Tschöp, Matthias H · Review
RPEP-00844 · 2003POMC-derived beta-endorphin selectively modulated the appetitive (wanting/seeking) phase of feeding behavior in a deprivation-state-dependent manner, separating opioid reward from hunger-driven consumption.
Low, Malcolm J; Hayward, Michael D; Appleyard, Suzanne M; Rubinstein, Marcelo · Animal Study
RPEP-00848 · 2003Chronic oral GHRP-2 in GH-deficient adults produced persistent increases in appetite and body weight alongside GH/IGF-1 elevation, confirming sustained orexigenic effects of long-term GH secretagogue therapy.
Mericq, Verónica; Cassorla, Fernando; Bowers, Cyril Y; Avila, Alejandra; Gonen, Boas; Merriam, George R · Clinical Trial
RPEP-00852 · 2003Ghrelin treatment improved LVEF, increased lean body mass, enhanced exercise capacity, and reduced neurohormonal activation in heart failure, simultaneously addressing cardiac dysfunction and cachexia.
Nagaya, Noritoshi; Kangawa, Kenji · Review
RPEP-00884 · 2004ICV beta-endorphin decreased blood pressure in lean rats but increased it in diet-induced obese rats, with enhanced sympathetic activation and reduced vagal tone — demonstrating a fundamental opioid-cardiovascular control reversal in obesity.
Barnes, Maria J; Jen, K-L Catherine; Dunbar, Joseph C · Animal Study
RPEP-00885 · 2004Intestinal fat is the most potent CCK-releasing macronutrient, with CCK mediating fat-induced satiety through vagal afferent and brain pathways — the primary mechanism for the high satiating power of dietary fat.
Beglinger, Christoph; Degen, Lukas · Review
RPEP-00901 · 2004CCK and GLP-1 are the most validated satiety biomarkers correlating with both subjective appetite ratings and actual food intake, with PYY, ghrelin, insulin, and glucose providing complementary information in multi-marker panels.
de Graaf, Cees; Blom, Wendy A M; Smeets, Paul A M; Stafleu, Annette; Hendriks, Henk F J · Review
RPEP-00906 · 2004At least 8 gut/pancreatic hormones regulate satiety, with GLP-1, PYY, and amylin identified as the most promising therapeutic targets for obesity — with combination therapy suggested for superior outcomes.
Druce, Maralyn R; Small, Caroline J; Bloom, Stephen R · Review
RPEP-00916 · 2004Ghrelin's integrated control of appetite, adiposity, and GnRH/gonadotropin secretion links eating disorders, obesity, and reproductive dysfunction through a common hormonal mechanism.
Gottero, C; Broglio, F; Prodam, F; Destefanis, S; Bellone, S; Benso, A; Gauna, C; Arvat, E; van der Lely, A J; Ghigo, E · Review
RPEP-00919 · 2004PYY3-36 inhibited food intake in MC4R knockout mice, demonstrating a melanocortin-4 receptor-independent satiety mechanism and establishing PYY as an independent appetite-suppressing pathway from the alpha-MSH system.
Halatchev, Ilia G; Ellacott, Kate L J; Fan, Wei; Cone, Roger D · Animal Study
RPEP-00921 · 2004Human appetite is regulated by a multi-level system including adiposity signals (leptin, insulin), gut peptides (GLP-1, PYY, CCK, ghrelin), and hypothalamic neuropeptides (NPY, AgRP, POMC), with GLP-1 and PYY identified as the most druggable targets.
Halford, Jason C G; Cooper, Gillian D; Dovey, Terence M · Review
RPEP-00923 · 2004Vagal stimulation amplified the inhibitory ghrelin response to oral fat in a human/animal model, demonstrating the vagus nerve acts as a gain controller for fat-induced ghrelin suppression — the gut-brain communication amplifying satiety.
Heath, R B; Jones, R; Frayn, K N; Robertson, M D · Animal Study
RPEP-00925 · 2004Normal, obese, and binge-eating individuals show distinct patterns of appetite signal dysfunction across peripheral (gut peptides, adipokines) and central (hypothalamic neuropeptide) systems — disorder-specific signaling profiles enabling targeted treatment.
Hellström, Per M; Geliebter, Allan; Näslund, Erik; Schmidt, Peter T; Yahav, Eric K; Hashim, Sami A; Yeomans, Martin R · Review
RPEP-00931 · 2004Hypothalamic feeding circuits operate through electrophysiological excitation of NPY/AgRP neurons (hunger) and inhibition of POMC/CART neurons (satiety), with peripheral signals (ghrelin, leptin, insulin) directly modulating neuronal firing patterns.
Jobst, Erin E; Enriori, Pablo J; Cowley, Michael A · Review
RPEP-00935 · 2004Food intake control operates through an integrated brain-gut axis where peripheral peptides (GLP-1, PYY, CCK, ghrelin, amylin) signal via vagal and hormonal routes to central circuits (NPY/AgRP, POMC/CART, CRF) for coordinated appetite regulation.
Konturek, S J; Konturek, J W; Pawlik, T; Brzozowski, T · Review
RPEP-00936 · 2004Ghrelin demonstrates validated multi-system functions: GH release, appetite/adiposity control, cardiovascular protection, immune modulation, gastric motility regulation, and reproductive function — through GHS-R and non-GHS-R pathways in virtually every organ system.
Korbonits, Márta; Goldstone, Anthony P; Gueorguiev, Maria; Grossman, Ashley B · Review