Gestational Diabetes Mellitus and Colostral Appetite-Regulating Adipokines.

Gestational diabetes mellitus (GDM) is a complex metabolic disorder that has short- and long-term effects on maternal and offspring health. This study aimed to assess the impact of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment) on colostral appetite-regulating molecules. Colostrum samples were collected from hyperglycemic (N = 30) and normoglycemic (N = 21) mothers, and the concentrations of milk hormones were determined by immunoenzymatic assay. A difference was found for milk ghrelin, but not for molecules such as adiponectin, leptin, resistin, or IGF-I levels, in relation to maternal hyperglycemia. The colostral ghrelin in the GDM-G1 cohort (0.21 ng/mL) was significantly lower than for GDM-G2 (0.38 ng/mL) and non-GDM groups (0.36 ng/mL). However, colostral resistin was higher, but not significantly, for GDM-G1 (13.33 ng/mL) and GDM-G2 (12.81 ng/mL) cohorts than for normoglycemic mothers (7.89 ng/mL). The lack of difference in relation to hyperglycemia for milk leptin, adiponectin, leptin-adiponectin ratio, resistin, and IGF-I levels might be the outcome of effective treatment of GDM during pregnancy. The shift between ghrelin and other appetite-regulating hormones might translate into altered ability to regulate energy balance, affecting offspring's metabolic homeostasis.

Food Cravings and Obesity in Women with Polycystic Ovary Syndrome: Pathophysiological and Therapeutic Considerations.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, constitutes a metabolic disorder frequently associated with obesity and insulin resistance (IR). Furthermore, women with PCOS often suffer from excessive anxiety and depression, elicited by low self-esteem due to obesity, acne, and hirsutism. These mood disorders are commonly associated with food cravings and binge eating. Hypothalamic signaling regulates appetite and satiety, deteriorating excessive food consumption. However, the hypothalamic function is incapable of compensating for surplus food in women with PCOS, leading to the aggravation of obesity and a vicious circle. Hyperandrogenism, IR, the reduced secretion of cholecystokinin postprandially, and leptin resistance defined by leptin receptors' knockout in the hypothalamus have been implicated in the pathogenesis of hypothalamic dysfunction and appetite dysregulation. Diet modifications, exercise, and psychological and medical interventions have been applied to alleviate food disorders, interrupting the vicious circle. Cognitive-behavioral intervention seems to be the mainstay of treatment, while the role of medical agents, such as GLP-1 analogs and naltrexone/bupropion, has emerged.

Deacetylated Konjac Glucomannan with a Slower Hydration Rate Delays Rice Digestion and Weakens Appetite Response.

The physical characteristics of chyme during gastrointestinal digestion are considered to significantly affect nutrient digestion and absorption (such as glucose diffusion), which has an impact on postprandial satiety. The present study aims to analyze the hydration rate (HR) and rheological properties of deacetylated konjac glucomannan (DKGM) at different degrees and then explore their effects on rice texture, digestive properties, and the subjects' post-meal appetite. The present results show that, as the deacetylation degree (DD) of KGM increased, the intersection point of the viscoelastic modulus shifted to a high shear rate frequency, and as the swelling time of the DKGM was prolonged, its HR decreased significantly. The results of the in vitro gastrointestinal digestion tests show that the hardness and chewability of the rice in the fast-hydration group (MK1) were remarkably reduced. In contrast, the slow-hydration group (MK5) exhibited an outstanding ability to resist digestion. The kinetics of starch hydrolysis revealed that the HR of the rice in the fast-hydration group was 1.8 times faster than that of the slow-hydration group. Moreover, it was found that the subjects' appetite after the meal was highly related to the HR of the MK. Their hunger (p < 0.001), desire to eat (p < 0.001), and prospective food consumption (p < 0.001) were significantly inhibited in the slow-hydration group (MK5) compared to the control. This study explored the nutritional effects of the hydration properties derived from the DKGM, which may contribute to modifying the high glycemic index food and provide ideas for the fabrication of food with enhanced satiating capacity.

Sensing stretch to suppress appetite.

Food intake activates a mechanosensitive ion channel that inhibits ghrelin production and reduces appetite.

Does intradialytic oral nutrition impact hemodialysis patients' quality of life, appetite, and safety? a pilot study of a crossover clinical trial / ¿La nutrición oral intradialítica impacta en la calidad de vida, el apetito y la seguridadde los pacientes en hemodiálisis? Estudio piloto de un ensayo clínico cruzado

Introduction: due to the catabolic characteristics of hemodialysis (HD), patients should consume foods or supplements during this treatment to meet their energy requirements and maintain a neutral nitrogen balance; however, there are some outcomes in which the effect of intradialytic oral nutrition (ION) is scarcely known. Objectives: this study aims to evaluate the effect of two types of ION (liquid and solid) on Quality of Life (QoL), appetite, and safety in HD patients. Methods: a pilot randomized, crossover clinical trial was performed in 18 patients on chronic HD. One group received ION for 18 HD sessions, after the crossover continued for 18 more sessions in the control group, and vice versa. We recorded QoL, appetite, systolic blood pressure (SBP), and intradialytic hypotension (IH) events. Results: clinical improvement was observed for most QoL components. Regardless of the consistency of supplementation, SBP increased to 4.10 mmHg. Both study groups reported a “very good-to-good” appetite. Conclusion: favorable clinical changes were observed in QoL scores during the study. Five of six IH events were reported for patients in the ION group, and SBP increased within the safe range (≤ 10 mmHg); appetite remained stable in both groups. Therefore, we concluded that this strategy, regardless of implementation consistency, is safe to be used in stable patients.(AU)

Introducción: debido a las características catabólicas de la hemodiálisis (HD), los pacientes deben consumir alimentos o suplementos durante este tratamiento para cubrir sus requerimientos energéticos y mantener un balance nitrogenado neutro; sin embargo, existen algunos desenlaces en los que el efecto de la nutrición oral intradialítica (NOID) es poco conocido.Objetivo: este estudio tiene como objetivo evaluar el efecto de dos tipos de NOID (líquido y sólido) sobre la calidad de vida, el apetito y la seguridad en pacientes en HD. Métodos: se realizó un estudio piloto en forma de ensayo clínico aleatorizado y cruzado con 18 pacientes en HD crónica. Un grupo recibió NOID durante 18 sesiones de HD, después del cruzamiento continuaron durante 18 sesiones más en el grupo de control, y viceversa. Se registraron la calidad de vida, el apetito, la presión arterial sistólica (PAS) y la hipotensión intradialítica (HI).Resultados: se observó mejoría clínica en la mayoría de los componentes de la calidad de vida. Independientemente de la consistencia de la suplementación, la PAS aumentó hasta 4,10 mmHg. Ambos grupos de estudio informaron de un apetito "muy bueno-bueno". Conclusiones: se observaron cambios clínicos favorables en las puntuaciones de calidad de vida durante el estudio. Cinco de seis eventos de HI se reportaron en pacientes del grupo de NOID y la PAS aumentó dentro del rango seguro (≤ 10 mmHg); el apetito se mantuvo estable en ambos grupos. Por lo tanto, se puede concluir que esta estrategia, independientemente de la consistencia implementada, es segura para ser utilizada en pacientes estables.(AU)

[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexiaâ ¡ (J-EPOCCâ ¡)-Challenges in Early Detection and Early Intervention for Appetite Loss and Weight Loss During Cancer Treatment].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC), conducted among cancer patients, their families and healthcare professionals in Japan showed that nearly half of patients who had experienced appetite loss or weight loss during cancer treatment had not consulted with healthcare professionals about their symptoms, and it meant that patients missed the opportunity to receive medical intervention. Since anamorelin was approved in 2021 fo"r Cancer cachexia in non- small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCCⅡ)was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their family and healthcare professionals. The results showed that there was no apparent change in awareness of appetite loss and weight loss, suggesting many patients may miss treatment opportunities. Further disease awareness is required among patients and their families to enhance the understanding of the significance of therapeutic interventions for appetite loss or weight loss, and to call their attention for early detection and treatment.

Possible association between oral health status and appetite loss in community-dwelling older adults.

This study aimed to evaluate the association between the oral health status and appetite in community-dwelling older adults. We enrolled 100 people aged ≥65 years who had participated in long-term care prevention projects between December 2018 and January 2019. Appetite was assessed using the Council on Nutrition Appetite Questionnaire score. The oral health status was assessed based on the number of teeth, occlusal condition, swallowing function, tongue coating, and the Oral Health Assessment Tool. A multiple linear regression analysis was performed with appetite as the dependent variable and each variable related to oral health status as an independent variable. The analysis was adjusted for sex, age, activities of daily living, cognitive function, smoking habit, and alcohol consumption. Dental pain was associated with poor appetite in community-dwelling older adults. No other oral health status parameter was associated with appetite. Thus, controlling dental pain is critical to prevent appetite loss while considering other factors.

Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity-a randomised crossover trial from the SWEET consortium.

BACKGROUND: Sweeteners and sweetness enhancers (S&SE) are used to replace energy yielding sugars and maintain sweet taste in a wide range of products, but controversy exists about their effects on appetite and endocrine responses in reduced or no added sugar solid foods. The aim of the current study was to evaluate the acute (1 day) and repeated (two-week daily) ingestive effects of 2 S&SE vs. sucrose formulations of biscuit with fruit filling on appetite and endocrine responses in adults with overweight and obesity. METHODS: In a randomised crossover trial, 53 healthy adults (33 female, 20 male) with overweight/obesity in England and France consumed biscuits with fruit filling containing 1) sucrose, or reformulated with either 2) Stevia Rebaudioside M (StRebM) or 3) Neotame daily during three, two-week intervention periods with a two-week washout. The primary outcome was composite appetite score defined as [desire to eat + hunger + (100 - fullness) + prospective consumption]/4. FINDINGS: Each formulation elicited a similar reduction in appetite sensations (3-h postprandial net iAUC). Postprandial insulin (2-h iAUC) was lower after Neotame (95% CI (0.093, 0.166); p < 0.001; d = -0.71) and StRebM (95% CI (0.133, 0.205); p < 0.001; d = -1.01) compared to sucrose, and glucose was lower after StRebM (95% CI (0.023, 0.171); p < 0.05; d = -0.39) but not after Neotame (95% CI (-0.007, 0.145); p = 0.074; d = -0.25) compared to sucrose. There were no differences between S&SE or sucrose formulations on ghrelin, glucagon-like peptide 1 or pancreatic polypeptide iAUCs. No clinically meaningful differences between acute vs. two-weeks of daily consumption were found. INTERPRETATION: In conclusion, biscuits reformulated to replace sugar using StRebM or Neotame showed no differences in appetite or endocrine responses, acutely or after a two-week exposure, but can reduce postprandial insulin and glucose response in adults with overweight or obesity. FUNDING: The present study was funded by the Horizon 2020 program: Sweeteners and sweetness enhancers: Impact on health, obesity, safety and sustainability (acronym: SWEET, grant no: 774293).

Does intradialytic oral nutrition impact hemodialysis patients' quality of life, appetite, and safety? A pilot study of a crossover clinical trial.

Introduction: Introduction: due to the catabolic characteristics of hemodialysis (HD), patients should consume foods or supplements during this treatment to meet their energy requirements and maintain a neutral nitrogen balance; however, there are some outcomes in which the effect of intradialytic oral nutrition (ION) is scarcely known. Objectives: this study aims to evaluate the effect of two types of ION (liquid and solid) on Quality of Life (QoL), appetite, and safety in HD patients. Methods: a pilot randomized, crossover clinical trial was performed in 18 patients on chronic HD. One group received ION for 18 HD sessions, after the crossover continued for 18 more sessions in the control group, and vice versa. We recorded QoL, appetite, systolic blood pressure (SBP), and intradialytic hypotension (IH) events. Results: clinical improvement was observed for most QoL components. Regardless of the consistency of supplementation, SBP increased to 4.10 mmHg. Both study groups reported a "very good-to-good" appetite. Conclusion: favorable clinical changes were observed in QoL scores during the study. Five of six IH events were reported for patients in the ION group, and SBP increased within the safe range (≤ 10 mmHg); appetite remained stable in both groups. Therefore, we concluded that this strategy, regardless of implementation consistency, is safe to be used in stable patients.

Introducción: Introducción: debido a las características catabólicas de la hemodiálisis (HD), los pacientes deben consumir alimentos o suplementos durante este tratamiento para cubrir sus requerimientos energéticos y mantener un balance nitrogenado neutro; sin embargo, existen algunos desenlaces en los que el efecto de la nutrición oral intradialítica (NOID) es poco conocido. Objetivo: este estudio tiene como objetivo evaluar el efecto de dos tipos de NOID (líquido y sólido) sobre la calidad de vida, el apetito y la seguridad en pacientes en HD. Métodos: se realizó un estudio piloto en forma de ensayo clínico aleatorizado y cruzado con 18 pacientes en HD crónica. Un grupo recibió NOID durante 18 sesiones de HD, después del cruzamiento continuaron durante 18 sesiones más en el grupo de control, y viceversa. Se registraron la calidad de vida, el apetito, la presión arterial sistólica (PAS) y la hipotensión intradialítica (HI). Resultados: se observó mejoría clínica en la mayoría de los componentes de la calidad de vida. Independientemente de la consistencia de la suplementación, la PAS aumentó hasta 4,10 mmHg. Ambos grupos de estudio informaron de un apetito "muy bueno-bueno". Conclusiones: se observaron cambios clínicos favorables en las puntuaciones de calidad de vida durante el estudio. Cinco de seis eventos de HI se reportaron en pacientes del grupo de NOID y la PAS aumentó dentro del rango seguro (≤ 10 mmHg); el apetito se mantuvo estable en ambos grupos. Por lo tanto, se puede concluir que esta estrategia, independientemente de la consistencia implementada, es segura para ser utilizada en pacientes estables.

Depraved appetite in dromedary camels: Clinical, ultrasonographic, and postmortem findings.

Background: Camels are subjected to a wide variety of nutritional deficiencies as they are largely dependent upon grazing desert plants. As a consequence, the syndrome of pica or depraved appetite is occasionally seen in dromedary camels. The condition is manifested as chewing or eating abnormal things such as wood, dirt, bones, stones, clothes, plastics, mud, sand, or other inanimate objects. Aim: This study was designed to investigate the clinical, ultrasonographic, and postmortem findings in dromedary camels with pica or depraved appetite. Methods: Twenty-five camels of 5 days to 15 years were examined. Owner complaints included depraved appetite, loss of body condition, regurgitation of stomach content, and partial or complete absence of feces. Symptoms described were present for a period varying between 3 days, up to 12 months. The stomach compartments and small and large intestines were scanned using ultrasonography from the right and left sides of the abdomen. Necropsy was carried out on six female and three male camels where the thoracic and abdominal organs were examined with special attention to the digestive system. Results: The affected animals had a history of gradual loss of body conditions, eating foreign objects, decreased or total absence of feces, and regurgitation of stomach content. Using ultrasound, the foreign body was imaged occluding completely or partially the intestines. Foreign bodies within the rumen could not be visualized with ultrasound. In cases where the rumen is impacted by sand, small pin-points revealing acoustic enhancement were imaged. Foreign bodies were removed from the rumen at exploratory rumenotomy (n = 11), laparotomy (n = 3), or at necropsy (n = 8) in the form of plastics, cloths, sand, mud, wool balls, robes, glasses, or even metallic objects which may be blunt or sharp. Sixteen (64%) of the camels were recovered while the remaining 9 (36%) did not survive. Conclusion: The syndrome of pica or depraved appetite is an important condition in dromedary resulting in the ingestion of objects other than normal feed. Substantial economic losses are expected as a result of this syndrome. Ultrasonography of the digestive system may help the clinician in some cases to localize of occluding foreign bodies in the intestines, while in the transabdominal scanning of the stomach is valuable only in cases of sand impaction.

Gut hormones and appetite regulation.

PURPOSE OF REVIEW: Various gut hormones interact with the brain through delicate communication, thereby influencing appetite and subsequent changes in body weight. This review summarizes the effects of gut hormones on appetite, with a focus on recent research. RECENT FINDINGS: Ghrelin is known as an orexigenic hormone, whereas glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), postprandial peptide YY (PYY), and oxyntomodulin (OXM) are known as anorexigenic hormones. Recent human studies have revealed that gut hormones act differently in various systems, including adipose tissue, beyond appetite and energy intake, and even involve in high-order thinking. Environmental factors including meal schedule, food contents and quality, type of exercise, and sleep deprivation also play a role in the influence of gut hormone on appetite, weight change, and obesity. Recently published studies have shown that retatrutide, a triple-agonist of GLP-1, GIP, and glucagon receptor, and orforglipron, a GLP-1 receptor partial agonist, are effective in weight loss and improving various metabolic parameters associated with obesity. SUMMARY: Various gut hormones influence appetite, and several drugs targeting these receptors have been reported to exert positive effects on weight loss in humans. Given that diverse dietary and environmental factors affect the actions of gut hormones and appetite, there is a need for integrated and largescale long-term studies in this field.

Effect of inulin on breath hydrogen, postprandial glycemia, gut hormone release, and appetite perception in RYGB patients: a prospective, randomized, cross-over pilot study.

BACKGROUND AND OBJECTIVE: Large intestinal fermentation of dietary fiber may control meal-related glycemia and appetite via the production of short-chain fatty acids (SCFA) and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We investigated whether this mechanism contributes to the efficacy of the Roux-en-Y gastric bypass (RYGB) by assessing the effect of oligofructose-enriched inulin (inulin) vs. maltodextrin (MDX) on breath hydrogen (a marker of intestinal fermentation), plasma SCFAs, gut hormones, insulin and blood glucose concentrations as well as appetite in RYGB patients. METHOD: Eight RYGB patients were studied on two occasions before and ~8 months after surgery using a cross-over design. Each patient received 300 ml orange juice containing 25 g inulin or an equicaloric load of 15.5 g MDX after an overnight fast followed by a fixed portion snack served 3 h postprandially. Blood samples were collected over 5 h and breath hydrogen measured as well as appetite assessed using visual analog scales. RESULTS: Surgery increased postprandial secretion of GLP-1 and PYY (P ≤ 0.05); lowered blood glucose and plasma insulin increments (P ≤ 0.05) and reduced appetite ratings in response to both inulin and MDX. The effect of inulin on breath hydrogen was accelerated after surgery with an increase that was earlier in onset (2.5 h vs. 3 h, P ≤ 0.05), but less pronounced in magnitude. There was, however, no effect of inulin on plasma SCFAs or plasma GLP-1 and PYY after the snack at 3 h, neither before nor after surgery. Interestingly, inulin appeared to further potentiate the early-phase glucose-lowering and second-meal (3-5 h) appetite-suppressive effect of surgery with the latter showing a strong correlation with early-phase breath hydrogen concentrations. CONCLUSION: RYGB surgery accelerates large intestinal fermentation of inulin, however, without measurable effects on plasma SCFAs or plasma GLP-1 and PYY. The glucose-lowering and appetite-suppressive effects of surgery appear to be potentiated with inulin.

Influence of the gut microbiome on appetite-regulating neuropeptides in the hypothalamus: Insight from conventional, antibiotic-treated, and germ-free mouse models of anorexia nervosa.

Recent research highlights the profound impact of the gut microbiome on neuropsychiatric disorders, shedding light on its potential role in shaping human behavior. In this study, we investigate the role of the gut microbiome in appetite regulation using activity-based anorexia (ABA) mouse model of anorexia nervosa (AN) - a severe eating disorder with significant health consequences. ABA was induced in conventional, antibiotic-treated, and germ-free mice. Our results show the clear influence of the gut microbiome on the expression of four orexigenic (neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, and orexin) and four anorexigenic peptides (cocaine- and amphetamine-regulated transcript, corticotropin-releasing hormone, thyrotropin-releasing hormone, and pro-opiomelanocortin) in the hypothalamus. Additionally, we assessed alterations in gut barrier permeability. While variations were noted in germ-free mice based on feeding and activity, they were not directly attributable to the gut microbiome. This research emphasizes that the gut microbiome is a pivotal factor in AN's appetite regulation beyond just dietary habits or physical activity.

Gastric mechanosensitive channel Piezo1 regulates ghrelin production and food intake.

Ghrelin, produced mainly by gastric X/A-like cells, triggers a hunger signal to the central nervous system to stimulate appetite. It remains unclear whether X/A-like cells sense gastric distention and thus regulate ghrelin production. Here we show that PIEZO1 expression in X/A-like cells decreases in patients with obesity when compared to controls, whereas it increases after sleeve gastrectomy. Male and female mice with specific loss of Piezo1 in X/A-like cells exhibit hyperghrelinaemia and hyperphagia and are more susceptible to overweight. These phenotypes are associated with impairment of the gastric CaMKKII/CaMKIV-mTOR signalling pathway. Activation of PIEZO1 by Yoda1 or gastric bead implantation inhibits ghrelin production, decreases energy intake and induces weight loss in mice. Inhibition of ghrelin production by Piezo1 through the CaMKKII/CaMKIV-mTOR pathway can be recapitulated in a ghrelin-producing cell line mHypoE-42. Our study reveals a mechanical regulation of ghrelin production and appetite by PIEZO1 of X/A-like cells, which suggests a promising target for anti-obesity therapy.

Brain sodium sensing for regulation of thirst, salt appetite, and blood pressure.

The brain possesses intricate mechanisms for monitoring sodium (Na) levels in body fluids. During prolonged dehydration, the brain detects variations in body fluids and produces sensations of thirst and aversions to salty tastes. At the core of these processes Nax , the brain's Na sensor, exists. Specialized neural nuclei, namely the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which lack the blood-brain barrier, play pivotal roles. Within the glia enveloping the neurons in these regions, Nax collaborates with Na+ /K+ -ATPase and glycolytic enzymes to drive glycolysis in response to elevated Na levels. Lactate released from these glia cells activates nearby inhibitory neurons. The SFO hosts distinct types of angiotensin II-sensitive neurons encoding thirst and salt appetite, respectively. During dehydration, Nax -activated inhibitory neurons suppress salt-appetite neuron's activity, whereas salt deficiency reduces thirst neuron's activity through cholecystokinin. Prolonged dehydration increases the Na sensitivity of Nax via increased endothelin expression in the SFO. So far, patients with essential hypernatremia have been reported to lose thirst and antidiuretic hormone release due to Nax -targeting autoantibodies. Inflammation in the SFO underlies the symptoms. Furthermore, Nax activation in the OVLT, driven by Na retention, stimulates the sympathetic nervous system via acid-sensing ion channels, contributing to a blood pressure elevation.

Gengricin®: A Nutraceutical Formulation for Appetite Control and Therapeutic Weight Management in Adults Who Are Overweight/Obese.

In the field of nutritional science and metabolic disorders, there is a growing interest in natural bitter compounds capable of interacting with bitter taste receptors (TAS2Rs) useful for obesity management and satiety control. This study aimed to evaluate the effect of a nutraceutical formulation containing a combination of molecules appropriately designed to simultaneously target and stimulate these receptors. Specifically, the effect on CCK release exerted by a multi-component nutraceutical formulation (Cinchona bark, Chicory, and Gentian roots in a 1:1:1 ratio, named Gengricin®) was investigated in a CaCo-2 cell line, in comparison with Cinchona alone. In addition, these nutraceutical formulations were tested through a 3-month randomized controlled trial (RCT) conducted in subjects who were overweight-obese following a hypocaloric diet. Interestingly, the Gengricin® group exhibited a significant greater weight loss and improvement in body composition than the Placebo and Cinchona groups, indicating its effectiveness in promoting weight regulation. Additionally, the Gengricin® group reported higher satiety levels and a significant increase in serum CCK levels, suggesting a physiological basis for the observed effects on appetite control. Overall, these findings highlight the potential of natural nutraceutical strategies based on the combination of bitter compounds in modulating gut hormone release for effective appetite control and weight management.

Effects of unstable ß-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2.

Amino acyl-tRNA synthetases perform diverse non-canonical functions aside from their essential role in charging tRNAs with their cognate amino acid. The phenylalanyl-tRNA synthetase (PheRS/FARS) is an α2ß2 tetramer that is needed for charging the tRNAPhe for its translation activity. Fragments of the α-subunit have been shown to display an additional, translation-independent, function that activates growth and proliferation and counteracts Notch signalling. Here we show in Drosophila that overexpressing the ß-subunit in the context of the complete PheRS leads to larval roaming, food avoidance, slow growth, and a developmental delay that can last several days and even prevents pupation. These behavioural and developmental phenotypes are induced by PheRS expression in CCHa2+ and Pros+ cells. Simultaneous expression of ß-PheRS, α-PheRS, and the appetite-inducing CCHa2 peptide rescued these phenotypes, linking this ß-PheRS activity to the appetite-controlling pathway. The fragmentation dynamic of the excessive ß-PheRS points to ß-PheRS fragments as possible candidate inducers of these phenotypes. Because fragmentation of human FARS has also been observed in human cells and mutations in human ß-PheRS (FARSB) can lead to problems in gaining weight, Drosophila ß-PheRS can also serve as a model for the human phenotype and possibly also for obesity.

The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake.

Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY3-36 preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY3-36, but not peripherally administered pharmacological doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is not evident in the germline model. Loss of vagal Y2R signalling also results in altered meal patterning associated with accelerated gastric emptying. These results are important for the design of PYY-based anti-obesity agents.