Peptide YY

Assessment of serum concentrations of the "satiety hormone" - peptide YY concentration in body weight disorders in girls with anorexia nervosa and obesity.

Katarzyna Gołąb-Jenerał, Małgorzata Blaska, Karolina Ziora-Jakutowicz +3 more

Peptide YY (PYY), a key satiety hormone, exhibits altered serum concentrations in body weight disorders, although its role remains debated. Conflicting adult studies highlight the need to clarify PYY 1-36 dynamics in pediatric populations with anorexia nervosa (AN) and obesity (OB).

Physical activity promotes gut adaptation, nutrient responsiveness, and sensitivity to gut peptides in male mice.

Cecilie Bæch-Laursen, Jon Vergara Ucin, Katrine Douglas Galsgaard +6 more

Physical activity helps maintain a healthy stable body weight. One mechanism underlying this beneficial effect could be the improved coupling between energy intake and expenditure, since hunger and satiety are better regulated in active individuals. Whether this enhancement of appetite control by exercise is reflected in overall adaptations in the gut and gut-brain communication remains poorly defined.

Sex-based differences in the enteroendocrine system and food intake regulation due to dietary protein replacement by Alphitobius Diaperinus in rats.

Oria Soler, Mònica Lores, Esther Rodríguez-Gallego +6 more

The rising global demand for animal protein, coupled with the environmental impact of conventional livestock, has sparked interest in sustainable alternatives. Insect-derived proteins, particularly from Alphitobius diaperinus (lesser mealworm), offer high nutritional value, good digestibility, and a minimal ecological footprint. Enteroendocrine hormones such as ghrelin, peptide YY (PYY), cholecystokinin (CCK), and glucagon-like peptide-1 (GLP-1) are key regulators of appetite, satiety, and energy homeostasis, responding dynamically to the composition and quality of ingested nutrients. Given the increasing prevalence of protein malnutrition in aging population and the metabolic challenges posed by obesogenic diets, this study aimed to investigate whether the enteroendocrine-modulating effects previously observed with acute A. diaperinus administration are sustained when utilized as the sole dietary protein source. Furthermore, we evaluated sex-specific responses under both standard and high-fat diet conditions in rats. Our findings demonstrate that A. diaperinus-based diets can alter caloric intake and elicit differential enteroendocrine secretion patterns depending on the sex and metabolic status of the animal, suggesting context-specific regulatory effects on energy balance and gut hormone responses. Together, these results enhance our understanding of how insect-based proteins interact with nutrient-sensing pathways and may inform the development of targeted nutritional strategies to support healthy aging, metabolic health, and environmental sustainability.

Acute L-Leucine Supplementation and Sprint Exercise Elicit Distinct Appetite and Inflammatory Responses in Persons with Overweight: A Randomized, Counterbalanced, and Crossover Design Study.

Elias de França, Ronaldo Vagner Thomatieli-Santos, Rita de Cássia Aquino +7 more

Our objective was to evaluate the acute effect of L-leucine supplementation and high-intensity sprint exercise on appetite-controlling neuropeptides and their association with the subjective perception of appetite (SPA), satiety (SPS), food intake, and inflammatory response in overweight participants.

Migrant blackbirds (Turdus merula) on stopover have higher plasma PYY compared to residents: A validation and proof-of-concept.

Alexander T Baugh, Jesko Partecke, Natalie Wellbrock +5 more

Migratory birds expend substantial energy during flight and often rely on stopovers to refuel. Foraging behavior during stopover might vary with fuel loss and food availability though likely involves higher food intake rates than in non-migratory (resident) individuals. In mammals, hormones such as leptin signal information about energy balance and satiety. In contrast the gut hormone peptide YY (PYY), which rises rapidly after feeding and suppresses appetite in mammals, might serve a similar functional role in songbirds, which lack functional leptin. We validated and measured plasma PYY in migrant and resident Common Blackbirds (Turdus merula) on Helgoland, a key North Sea stopover site, during peak autumn migration. Migrants exhibited significantly higher circulating PYY levels than residents, possibly reflecting increased or differential foraging. PYY was unrelated to body condition or fat stores. This proof of concept study justifies future work on plasma PYY and other metabolic signals and their potential influence on avian migratory decision making.

Phascolarctobacterium faecium reduces food intake via PYY signaling, contributing to the mitigation of body weight gain in diet-induced obese mice.

Clara Bullich-Vilarrubias, Marina Romaní-Pérez, Inmaculada López-Almela +6 more

Excess energy intake contributes to adiposity in obesity. We investigated whether the human intestinal bacterium Phascolarctobacterium faecium could prevent obesity via enteroendocrine pathways in a mouse model of diet-induced obesity (DIO). Daily administration of P. faecium (2 × 109 cells/mouse) reduced food intake through the early overproduction of the satiety hormone peptide YY (PYY) compared to untreated DIO mice. Moreover, P. faecium increased the intestinal levels of branched-chain amino acids, which, in turn, stimulated PYY secretion in neuroendocrine cell cultures and also modified gut microbiota composition. A pair-feeding study demonstrated that the anorexigenic effect of P. faecium contributes to its effects in attenuating body weight gain in DIO mice, but that other mechanisms are also involved in its metabolic benefits. Specifically, P. faecium accelerated gut transit and serum lipid clearance, thereby limiting adiposity independently of food intake. This study identifies the mode of action of a human intestinal bacterium recently linked to obesity protection, providing valuable insights into host-microbe interactions governing body weight.

The effect of consuming different dietary protein sources at breakfast upon self rated satiety, peptide YY, glucagon like peptide-1, and subsequent food intake in young and older adults.

Anthony W Watson, Anna Brooks, Lucy Moore +2 more

Interest in plant-based protein in the UK is increasing due to health, environmental, and ethical considerations. Recent studies have explored how different protein sources impact satiety and related gut hormone responses, with evidence suggesting varied responses between animal-based and plant-based proteins. Skewed protein intake patterns, especially at breakfast, present an opportunity for improving dietary protein distribution in populations who may require increased protein intake but often face appetite reductions. This study determined the acute effect of consuming a plant-based, high protein drink containing 30 g of protein (HPDp); an animal-based, high protein breakfast containing 30 g of protein (HPBa); and a low-protein (10 g), high-carbohydrate breakfast (HCLPB) on satiety hormone responses, subjective appetite and subsequent energy intake in older and younger populations when consumed at breakfast. Eighteen heathy adults completed this within-subject, counterbalanced, cross-over study, (12 under 35 years of age and six over 65 years of age). Measurements for appetite were obtained at baseline, 30, 60, 90, 120, 150, 180, 210 and 240 min, and plasma, GLP-1 and PYY at baseline, 30, 60, 90, 120, 180 min post breakfast consumption. No difference in appetitive responses was found between the HPDp and the energy- and protein-matched HPBa, with both eliciting greater GLP-1 and PYY (both p < 0.004) responses compared with a high carbohydrate, low protein meal. Subjective appetite was also suppressed to a greater extent with HPDp compared with HCLPB (p = 0.001). No differences were observed in ad libitum energy intake.

Initial and evolutionary profile of adverse responders to an intensive weight loss intervention: the RESOLVE Study.

Mélina Bailly, Laurie Isacco, Frédéric Dutheil +14 more

There is a need to better identify adverse responders to weight-loss interventions. The aim of this study was to: 1) identify potential predictive factors of adverse responders to weight loss; and 2) follow their long-term evolution.

Microplastics affect food intake and the expression of appetite regulators and nutrient transporters in pond loach (Misgurnus anguillicaudatus).

Thanushanthahi Loganathan, Julianna Dyke, Helene Volkoff

Microplastics (MPs) are emerging pollutants in freshwater ecosystems, posing risks to aquatic organisms. This study examines the effects of dietary MP exposure on food intake, appetite regulation, and nutrient transporter expression in pond loach (Misgurnus anguillicaudatus), a sediment-feeding facultative air breathing freshwater fish. Fish were exposed to small (250-300 μm), medium (425-500 μm), and large (710-850 μm) polyethylene microspheres for two weeks. Food intake was significantly reduced in fish fed small and medium MPs, but not large MPs, suggesting size-dependent ingestion effects. In the brain, MP (425-500 μm) exposure suppressed orexin expression, a key appetite-stimulating neuropeptide, while other central appetite regulators remained unchanged. In the anterior intestine, anorexigenic peptides such as cholecystokinin (cck) and peptide YY (pyy) were upregulated, alongside glucose-dependent insulinotropic polypeptide (gip), indicating enhanced satiety signaling. Sodium-dependent glucose transporter 1 (slc5a1) expression was downregulated, suggesting impaired glucose absorption. MPs induced upregulation of gip and urea transporter 2 (slc14a2) in the mid intestine, and pyy, gip, glucose transporter 1 (slc2a1), urea transporter 2 and hypoxia-inducible factor 1α (hif1a) in the posterior intestine. These results show that MP exposure disrupts feeding, alters endocrine signaling, and affects nutrient absorption in pond loach, highlighting the physiological sensitivity of sediment-feeding fish to MP contamination and the ecological risks posed by plastic pollution to aquatic species and ecosystems.

Acute Exercise Effects on Appetite and Energy Intake in People Living With Overweight and Obesity: A Systematic Review and Meta-Analysis.

Nan Li, Min Wu, Yanchun Li

Overweight and obesity are associated with dysregulation of appetite-related hormones and altered energy intake. Exercise has been proposed as a strategy to modulate appetite and support weight management. A comprehensive search of databases, including Web of Science, PubMed, Scopus, Google Scholar, ScienceDirect, Academic Search Premier, and EBSCOHost, identified 19 studies (34 trials) for inclusion. Using a random-effects model, we calculated effect sizes (ES) for hormone concentration, appetite perception, and energy intake. Acute exercise exerted a moderate suppressive effect on acylated ghrelin (ES = -0.73) and a moderate, nonsignificant effect on insulin (ES = -0.55). A large but nonsignificant increase was observed for glucagon-like peptide-1 (ES = 3.96), while peptide YY showed a small, nonsignificant increase (ES = 0.24). Exercise significantly reduced hunger (ES = -0.35) and prospective food consumption (ES = -0.26), with minimal effects on fullness (ES = 0.16) and satiety (ES = 0.15). Significant reductions were found in both relative (ES = -0.54) and absolute energy intake (ES = -0.19). Exercise may be an effective short-term intervention for reducing appetite and energy intake among people living with overweight and obesity. Registration: PROSPERO CRD42024623903.

Upper-gastrointestinal tract metabolite profile regulates glycaemic and satiety responses to meals with contrasting structure: a pilot study.

Mingzhu Cai, Shilpa Tejpal, Martina Tashkova +12 more

Dietary interventions to combat non-communicable diseases focus on optimizing food intake but overlook the influence of food structure. Here, we investigate how food structure influences digestion. In a randomized crossover study, ten healthy participants were fitted with nasoenteric tubes that allow simultaneous gastric and duodenal sampling, before consuming iso-nutrient chickpea meals with contrasting cellular structures. The primary outcome is gut hormone response. Secondary outcomes are intestinal content analysis, blood glucose and insulin response, subjective appetite changes and ad libitum energy intake. We show that the 'Broken' and 'Intact' cell structures of meals result in different digestive and metabolomic profiles, leading to distinct postprandial gut hormones, glycaemia and satiety responses. 'Broken' meal structure elicits higher glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and blood glycaemia, driven by high starch digestibility and a sharp rise in gastric maltose within 30 min. 'Intact' meal structure produces a prolonged release of glucagon-like peptide-1 and peptide-YY, elevated duodenal amino acids and undigested starch at 120 min. This work highlights how food structure alters upper gastrointestinal nutrient-sensing hormones, providing insights into the adverse effects of modern diets on obesity and type 2 diabetes. ISRCTN registration: ISRCTN18097249.

Isoenergetic reduction of dietary macronutrients affects body composition, physical activity, and post-prandial hormone responses in lean and obese cats fed to maintain body weight.

Hannah Godfrey, Érico de Mello Ribeiro, Shoshana Verton-Shaw +5 more

High consumption of dietary carbohydrates (nitrogen-free extract, NFE) in extruded dry foods is postulated as a risk factor for feline obesity, though evidence is limited. This study utilized a three-test diet approach to isolate the effect of each macronutrient on body composition, voluntary physical activity, and serum satiety hormone response in lean and obese cats.

Prebiotics pectin and resistant starch-type 4 stimulate peptide YY and cholecystokinin to promote satiety, and improve gut microbiota composition.

Souvik Patra, Savana L Everhart Nunn, Gizem Levent +1 more

Dietary prebiotics pectin and resistant starch type-4 (RS-4) promote satiety and alter gut microbiota; however, the underlying neurohormonal mechanisms of satiety remain poorly understood. We determined the effects of pectin, RS-4, and their combination on energy balance and gut microbiota composition, and assessed whether the gut hormones peptide YY (PYY) and cholecystokinin (CCK) play a role in fiber-induced satiety. High-fat diet -induced obese male rats (n = 7-8/group) were fed either control, pectin, RS-4, or a combination of pectin and RS-4 diet. We found that pectin, RS-4, and their combination decreased food intake. Pectin alone, or combined with RS-4, shifted substrate utilization towards fat and reduced gains in weight and adiposity. Pectin alone or combined with RS-4 enhanced the expression and plasma concentrations of PYY and CCK. Importantly, systemic blockade of PYY-Y2 and CCK-1 receptors attenuated the hypophagic effects of pectin, and CCK-1 receptor blockade partly attenuated the hypophagia from RS-4. The prebiotics significantly altered fecal β-diversity metrics, suggestive of improvements in gut microbiota composition. Pectin and RS-4 alone, or in combination, were associated with increased relative abundance of phylum Bacteroidota, decreased Firmicutes, and increased concentrations of amino acids and biogenic amines in feces. Collectively, these findings suggest that dietary pectin and RS-4 improved energy balance and gut microbiota composition, and importantly, demonstrated that the satiety effects of these diets were mediated, in part, via enhanced endogenous PYY and CCK signaling.

Objective and subjective appetite measures: high versus low eating frequency in a randomized crossover clinical trial.

Xiaochen Zhang, Martine Perrigue, Jeannette M Schenk +4 more

The objective of this study was to examine objective (ghrelin and peptide YY [PYY]) and subjective appetite measures following 21-day high and low eating frequency (EF) interventions among healthy adults.

Exogenous oral application of PYY and exendin-4 impacts upon taste-related behavior and taste perception in wild-type mice.

Satya Iyer, Jean-Pierre Montmayeur, Sergei Zolotukhin +1 more

Several gut peptides have been implicated in feeding and body mass accumulation. Glucagon-like peptide 1 (GLP-1) and peptide tyrosine-tyrosine (PYY) have been shown to mediate satiety and reduce food intake. While systemic administration of such peptides has been explored as a therapy for metabolic disease, the effects of these hormones on taste signaling should also be considered given the importance of taste to feeding decisions and considering the fact that components of these signaling systems are expressed in cells of the peripheral gustatory system. We previously demonstrated that genetic disruption of PYY signaling in mice can impact on taste responsiveness and feeding and that viral expression of PYY in the salivary glands of PYY knockout mice can rescue responsiveness. The present work uses adeno-associated virus-mediated salivary gland treatment with both GLP-1 receptor agonist exendin-4 and/or PYY encoding vectors to explore the effect of stimulating these orally present signaling systems on taste-related behavioral responsiveness in male wild-type mice with intact peptide signaling systems. Results showed a significant effect of salivary gland treatment on responsiveness to multiple taste qualities. Data gathered from taste bud cells in vitro suggest that these peptides directly influence the responsiveness of these primary sensory cells. Collectively, these findings show that taste perception can be modulated by the exogenous application of satiety peptides in wild-type mice and suggest that the taste bud is a promising substrate for food intake modulation.

Are post-exercise plasma glucose elevations involved in exercise-induced appetite suppression?

Derek P D Bornath, Seth F McCarthy, Jessica A L Tucker +3 more

Changes in glucose and insulin are potentially involved in the appetite-regulatory effects of exercise considering their role post-prandially. The purpose of this study was to examine whether glucose and insulin play a role in post-exercise appetite regulation. Twelve participants (M = 8; 26 ± 5 years) completed 3 experimental sessions in a systematically rotated randomized crossover design: (1) no-exercise control (CTRL); (2) moderate-intensity continuous training (MICT; 30 min, 70% maximal oxygen consumption (V̇O2max)); and (3) sprint interval training (SIT; 4 × 30 s "all-out" sprints, interspersed with 4 min rest). Plasma glucose, insulin, acylated ghrelin, active peptide tyrosine tyrosine (PYY), active glucagon-like peptide-1 (GLP-1), and overall appetite perceptions were measured pre-exercise, 0, 30, 60, and 120 min post-exercise. Energy intake was recorded the day before, of, and after experimental sessions. Glucose was elevated 0 min post-exercise (p < 0.097, d > 0.52) compared to CTRL with no differences between exercise bouts. Acylated ghrelin was suppressed by MICT (60, 120 min) and SIT (0, 30, 60, 120 min; p < 0.080, d > 0.56) compared to CTRL, while also suppressed in SIT compared to MICT at 30, 60, 120 min (p < 0.026, d > 0.74). GLP-1 was elevated following MICT (0, 30, and 60 min) and SIT (60 min; p < 0.094, d > 0.53) compared to CTRL and following MICT compared to SIT (0 min; p = 0.005, d = 1.03). Overall appetite was suppressed by SIT post-exercise (p < 0.058, d > 0.61) compared to CTRL and MICT, and by MICT 0 min post-exercise compared to CTRL (p = 0.036, d = 0.71). There were no exercise effects on insulin, PYY, or free-living energy intake (p > 0.217, ηp 2 < 0.130). Glucose and insulin do not appear to play a role in exercise-induced appetite suppression.

Effects of Isoflavone Intake on Energy Requirement, Satiety, and Body Composition of Neutered Adult Cats.

Ana Lúcia Yoshida da Silva Yamada, Mônica Estela Zambon Merenda, Layne Carolina Pereira +9 more

Isoflavones are composed of phytoestrogens (genistein and daidzein), which can be metabolized by cats. These compounds can promote the maintenance of lean body mass and control food intake. These effects are desirable in neutered animals, as they are predisposed to obesity. The objective of this study was to evaluate the effects of dietary supplementation of 1.0% isoflavone on the metabolizable energy intake, serum concentrations of satiety-related hormones and peptides, and body composition of neutered cats. Sixteen neutered adult cats were blocked by gender and divided into two groups (n = 8): the control group (CG) received a commercial diet, while the isoflavone group (IG) received the same diet supplemented by 1% of isoflavone for 99 days. Computed tomography was performed on the first and last experimental days to assess the animals' body composition. Satiety challenges were conducted on days 19 and 44. In the last day of the study, blood samples were collected to determine the concentration of insulin, ghrelin, leptin, peptide YY, and GLP-1. A statistical analysis was conducted using R software 3.5.2, considering both the interaction and individual effects of group and time (p < 0.05). The average intake of genistein in the IG was 0.75 ± 0.10 mg/kg body weight, and daidzein intake was 51.73 ± 7.05 mg/kg. No significant individual or interaction effects were observed for any of the analyzed variables. Therefore, the inclusion of 1.0% isoflavone in the diet did not affect the energy requirements, satiety responses, or body composition of neutered adult cats.

Dynamic Hydration and Viscosity Control of Konjac Glucomannan Enhance Long-Term Antiobesity Effects by Reducing Food Intake in High-Fat-Diet-Fed Mice.

Liping Guo, Wallace Yokoyama, Ling Chen +2 more

The purpose of this study was to investigate the necessity and importance of dynamic hydration rate and ultimate viscosity control of konjac glucomannan (KGM) for long-term antiobesity effects in C57BL/6J mice on high-fat (HF) diets. KGM supplementation effectively attenuated HF-diet-induced increases in body and tissue weights. The hydration rate and viscosity changes of KGM in the digestive tract were found to have marked impacts on antiobesity effects. KGM with medium hydration and viscosity slowed gastric emptying and intestinal transit, leading to prolonged presence in the lower ileum, increased satiety-related hormones (GLP-1 and PYY), and an 18.27% reduction in daily food intake over 10 weeks (p < 0.05). This resulted in the greatest reduction in weight gain among HF-fed mice. In contrast, KGM with faster hydration and higher viscosity provided only short-term satiety due to rapid dilution. Furthermore, KGM improved metabolic health and altered glycolipid metabolism gene transcription while enriching beneficial gut bacteria; however, no significant differences were observed among the KGM groups in these effects. These findings highlight that synchronizing KGM's hydration rate and viscosity with digestive processes is crucial for regulating satiety and achieving long-term weight loss.

Proteins and Peptides from Food Sources with Effect on Satiety and Their Role as Anti-Obesity Agents: A Narrative Review.

Anaís Ignot-Gutiérrez, Gloricel Serena-Romero, Daniel Guajardo-Flores +3 more

Obesity, clinically defined as a body mass index (BMI) of 30 kg/m2 or higher, is a medical condition characterized by the excessive accumulation of body fat, which can lead to adverse health consequences. As a global public health issue with an escalating prevalence, controlling appetite and satiety is essential for regulating energy balance and managing body weight. Dietary proteins and peptides have gained interest in their potential to prevent and treat obesity by modulating satiety signals. This narrative review analyzes scientific evidence highlighting the role of dietary proteins and peptides in regulating satiety signals and investigates their therapeutic potential in preventing and treating obesity.

Effects of time-restricted eating and low-carbohydrate diet on psychosocial health and appetite in individuals with metabolic syndrome: A secondary analysis of a randomized controlled trial.

Yixuan Zheng, Xin Wang, Jingya Wang +11 more

Time-restricted eating (TRE) and low-carbohydrate diet (LCD) can improve multiple cardiometabolic parameters in patients with metabolic syndrome (MetS), but their effects on psychosocial health and satiety are unclear. In this study, we aimed to evaluate the effects of TRE, LCD, and their combination (TRE + LCD) on quality of life (QoL), sleep, mood, appetite, and metabolic hormones in patients with MetS.

Acute Consumption of Cooked Green Banana Pulp Beverage (Musa cavendishii) Decreases Plasma Glucose in Healthy Women: A Cross-Sectional Controlled Study.

Lilia Zago, Heloisa Rodrigues Pessoa, Carolyne Pimentel Rosado +3 more

This study aimed at comparing the carbohydrate composition of three banana varieties (cv. Nanica, Nanicão, and Prata) and investigating the effect of a single dose of cooked green banana pulp beverage (GBPd) on plasma glycemic homeostasis indexes (glucose, PYY, GIP, insulin) and hunger and satiety sensation (visual analog scale-VAS). The bananas were classified according to the color scale. The fiber, total carbohydrate, and resistant starch (RS) were determined using validated methods. Glucose homeostasis indexes and hunger/satiety sensation were determined in ten healthy women in two stages before and after intake: (1) glucose solution (250 g/L); (2) one week later, consumption of the glucose solution plus 75 g/L of GBPd. Blood samples were collected twice in stage-1 and every 15 min for 2 h in stage-2. Cv. Nanicão was selected, because it presented a higher content in RS and dietary fiber on dry base than the other cultivars. Thus, it was used to test glycemic response. After 2 h of GBPd intake, no difference was observed in hunger/satiety sensation and plasma glycemic homeostasis indexes, except for a decrease in plasma glucose concentration (-15%, p = 0.0232) compared to stage-1. These results suggest that cv. Nanicão has a higher potential as a functional ingredient and can influence the reduction in the glycemic index of a meal compared to other cultivars. However, it had not a short-term effect on hormones GIP and PYY in healthy women. Further research is needed to understand the long-term effects and mechanisms of green banana on glycemic control and satiety.

A Diet Containing Animal Source Protein as Fresh, Lean Beef Is More Well Liked and Promotes Healthier Eating Behavior Compared with Plant-Based Alternatives in Women with Overweight.

Morgan L Braden, Jess A Gwin, Heather J Leidy

Despite limited evidence from intervention trials, replacing animal-source protein-rich foods with plant alternatives continues to be recommended as part of a healthy dietary pattern.

Augmented gut hormone response to feeding in older adults exhibiting low appetite.

Aygul Dagbasi, Jordan Warner, Victoria Catterall +5 more

Age-related changes in gut hormones may play a role in anorexia of ageing. The aim of this study was to determine concentrations of ghrelin, PYY, and GLP-1 in older adults exhibiting an anorexia of ageing phenotype. Thirteen older adults with healthy appetite (OA-HA; 8f, 75 ± 7 years, 26.0 ± 3.2 kg m-2), fifteen older adults with low appetite (OA-LA; 10f, 72 ± 7 years, 23.6 ± 3.1 kg m-2), and twelve young adults (YA; 6f, 22 ± 2 years, 24.4 ± 2.0 kg m-2) completed the study. Healthy appetite and low appetite were determined based on BMI, habitual energy intake, self-reported appetite, and laboratory-assessed ad libitum lunch intake. Participants provided a fasted measure of subjective appetite and blood sample (0 min) before consuming a standardised breakfast (450 kcal). Appetite was measured and blood samples were drawn throughout a 240-min rest period. At 240 min, an ad libitum lunch meal was consumed. Relative intake at lunch (expressed as percentage of estimated total energy requirement) was lower for OA-LA (19.8 ± 7.7%) than YA (41.5 ± 9.2%, p < 0.001) and OA-HA (37.3 ± 10.0%, p < 0.001). Ghrelin suppression was greater for OA-LA (net AUC, -78719 ± 74788 pg mL-1·240min-1) than both YA (-23899 ± 27733 pg mL-1·240min-1, p = 0.016) and OA-HA (-21144 ± 31161 pg mL-1·240min-1, p = 0.009). There were trends for higher GLP-1 concentrations in OA-LA compared with YA at 90 min (8.85 ± 10.4 pM vs. 1.88 ± 4.63 pM, p = 0.073) and 180 min (5.00 ± 4.71 pM vs. 1.07 ± 2.83 pM, p = 0.065). There was a trend for a greater PYY response for OA-LA compared with OA-HA (net AUC p = 0.062). "Anorexigenic response score" - a composite score of gut hormone responses to feeding - showed greater anorexigenic response in OA-LA, compared with YA and OA-HA. No differences were seen in subjective appetite. These observations suggest augmented anorexigenic responses of gut hormones to feeding may be causal mechanisms of anorexia of ageing.

Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice.

Naima S Dahir, Yijun Gui, Yanan Wu +8 more

The melanocortin-3 receptor (MC3R) regulates GABA release from agouti-related protein (AgRP) nerve terminals and thus tonically suppresses multiple circuits involved in feeding behavior and energy homeostasis. Here, we examined the role of the MC3R and the melanocortin system in regulating the response to various anorexigenic agents. The genetic deletion or pharmacological inhibition of the MC3R, or subthreshold doses of an MC4R agonist, improved the dose responsiveness to glucagon-like peptide 1 (GLP1) agonists, as assayed by inhibition of food intake and weight loss. An enhanced anorectic response to the acute satiety factors peptide YY (PYY3-36) and cholecystokinin (CCK) and the long-term adipostatic factor leptin demonstrated that increased sensitivity to anorectic agents was a generalized result of MC3R antagonism. We observed enhanced neuronal activation in multiple hypothalamic nuclei using Fos IHC following low-dose liraglutide in MC3R-KO mice (Mc3r-/-), supporting the hypothesis that the MC3R is a negative regulator of circuits that control multiple aspects of feeding behavior. The enhanced anorectic response in Mc3r-/- mice after administration of GLP1 analogs was also independent of the incretin effects and malaise induced by GLP1 receptor (GLP1R) analogs, suggesting that MC3R antagonists or MC4R agonists may have value in enhancing the dose-response range of obesity therapeutics.

A Randomized, Crossover Trial Assessing Appetite, Energy Metabolism, Blood Biomarkers, and Ad Libitum Food Intake Responses to a Mid-Morning Pecan Snack vs. an Equicaloric High-Carbohydrate Snack in Healthy Volunteers with Overweight/Obesity.

John C Peters, Jeanne Anne Breen, Zhaoxing Pan +2 more

The differential effects of pecans versus other popular snack foods on appetite and blood markers of metabolism and satiety have not been well studied. This study investigated the effects of a single mid-morning snack of pecans or tortilla chips on subjective appetite, food intake, blood measures of hormones and metabolites, and resting energy expenditure.

Appetite, food intake, and gut hormone responses to glycomacropeptide protein ingestion in older adults: A feasibility, acceptability, and pilot study.

Jordan Warner, Rachel Stocker, Kirsten Brandt +4 more

Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.

Illuminating the neuropeptide Y4 receptor and its ligand pancreatic polypeptide from a structural, functional, and therapeutic perspective.

Corinna Schüß, Victoria Behr, Annette G Beck-Sickinger

The neuropeptide Y4 receptor (Y4R), a rhodopsin-like G protein-coupled receptor (GPCR) and the hormone pancreatic polypeptide (PP) are members of the neuropeptide Y family consisting of four receptors (Y1R, Y2R, Y4R, Y5R) and three highly homologous peptide ligands (neuropeptide Y, peptide YY, PP). In this family, the Y4R is of particular interest as it is the only subtype with high affinity to PP over NPY. The Y4R, as a mediator of PP signaling, has a pivotal role in appetite regulation and energy homeostasis, offering potential avenues for the treatment of metabolic disorders such as obesity. PP as anorexigenic peptide is released postprandial from the pancreas in response to food intake, induces satiety signals and contributes to hamper excessive food intake. Moreover, this system was also described to be associated with different types of cancer: overexpression of Y4R have been found in human adenocarcinoma cells, while elevated levels of PP are related to the development of pancreatic endocrine tumors. The pharmacological relevance of the Y4R advanced the search for potent and selective ligands for this receptor subtype, which will be significantly progressed through the elucidation of the active state PP-Y4R cryo-EM structure. This review summarizes the development of novel PP-derived ligands, like Obinepitide as dual Y2R/Y4R agonist in clinical trials or UR-AK86c as small hexapeptide agonist with picomolar affinity, as well as the first allosteric modulators that selectively target the Y4R, e.g. VU0506013 as potent Y4R positive allosteric modulator or (S)-VU0637120 as allosteric antagonist. Here, we provide valuable insights into the complex physiological functions of the Y4R and PP and the pharmacological relevance of the system in appetite regulation to open up new avenues for the development of tool compounds for targeted therapies with potential applications in metabolic disorders.

Intestinal Acyl-CoA synthetase 5 (ACSL5) deficiency potentiates postprandial GLP-1 & PYY secretion, reduces food intake, and protects against diet-induced obesity.

John D Griffin, Ying Zhu, Andrew Reeves +2 more

In the small intestine, the products of digestion of dietary triacylglycerol (TAG), fatty acids (FA) and monoacylglycerol, are taken up by absorptive cells, enterocytes, for systemic energy delivery. These digestion products can also bind receptors on endocrine cells to stimulate the release of hormones capable of influencing systemic energy metabolism. The initial phase of intestinal FA absorption involves the acylation of FAs to acyl-CoA by the acyl-CoA long chain synthetase (ACSL) enzymes. ACSL5 is abundantly expressed in the small intestinal epithelium where it is the major ACSL isoform, contributing approximately 80% of total ACSL activity. In mice with whole body deficiency of ACSL5, the rate of dietary fat absorption is reduced and energy expenditure is increased. However, the mechanisms by which intestinal ACSL5 contributes to intestinal FA metabolism, enteroendocrine signaling, and regulation of energy expenditure remain undefined. Here, we test the hypothesis that intestinal ACSL5 regulates energy metabolism by influencing dietary fat absorption and enteroendocrine signaling.

Physiological Appetite Regulation and Bariatric Surgery.

Indra Ramasamy

Obesity remains a common metabolic disorder and a threat to health as it is associated with numerous complications. Lifestyle modifications and caloric restriction can achieve limited weight loss. Bariatric surgery is an effective way of achieving substantial weight loss as well as glycemic control secondary to weight-related type 2 diabetes mellitus. It has been suggested that an anorexigenic gut hormone response following bariatric surgery contributes to weight loss. Understanding the changes in gut hormones and their contribution to weight loss physiology can lead to new therapeutic treatments for weight loss. Two distinct types of neurons in the arcuate hypothalamic nuclei control food intake: proopiomelanocortin neurons activated by the anorexigenic (satiety) hormones and neurons activated by the orexigenic peptides that release neuropeptide Y and agouti-related peptide (hunger centre). The arcuate nucleus of the hypothalamus integrates hormonal inputs from the gut and adipose tissue (the anorexigenic hormones cholecystokinin, polypeptide YY, glucagon-like peptide-1, oxyntomodulin, leptin, and others) and orexigeneic peptides (ghrelin). Replicating the endocrine response to bariatric surgery through pharmacological mimicry holds promise for medical treatment. Obesity has genetic and environmental factors. New advances in genetic testing have identified both monogenic and polygenic obesity-related genes. Understanding the function of genes contributing to obesity will increase insights into the biology of obesity. This review includes the physiology of appetite control, the influence of genetics on obesity, and the changes that occur following bariatric surgery. This has the potential to lead to the development of more subtle, individualised, treatments for obesity.

Satiety: a gut-brain-relationship.

Ghinwa M Barakat, Wiam Ramadan, Ghaith Assi +1 more

Many hormones act on the hypothalamus to control hunger and satiety through various pathways closely associated with several factors. When food is present in the gastro intestinal (GI) tract, enteroendocrine cells (EECs) emit satiety signals such as cholecystokinin (CCK), glucagon like peptide-1 (GLP-1) and peptide YY (PYY), which can then communicate with the vagus nerve to control food intake. More specifically, satiety has been shown to be particularly affected by the GLP-1 hormone and its receptor agonists that have lately been acknowledged as a promising way to reduce weight. In addition, there is increasing evidence that normal flora is also involved in the peripheral, central, and reward system that impact satiety. Moreover, neurologic pathways control satiety through neurotransmitters. In this review, we discuss the different roles of each of the GLP-1 hormone and its agonist, gut microbiomes, as well as neurotransmitters and their interconnected relation in the regulation of body's satiety homeostasis.