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Aim: To elucidate the effects of ultra‐processed foods (UPFs) on body weight and ad libitum energy intake compared with non‐UPFs. Materials and Methods: In this randomized, open‐label crossover study conducted at the University of Tokyo Hospital, overweight/obese Japanese male participants were randomly assigned (1:1) to start the study with consumption of either UPFs or non‐UPFs for 1 week, followed by a 2‐week washout period, before crossing over to the alternate food diet for 1 week. Individuals with diabetes, hypertension or any other medical conditions who visited a hospital regularly were excluded. The meals were designed to be matched for the total energy and macronutrient levels. The primary outcome was the difference in the body weight change between the UPF and non‐UPF periods. The differences in the average daily energy intake and chewing frequency were assessed as one of the prespecified secondary outcomes. Results: Nine eligible participants were randomly assigned to start the study with either UPFs or non‐UPFs. All participants completed the study. During the UPF period, participants gained 1.1 kg more weight (95% confidence interval 0.2 to 2.0; P =.021) and consumed 813.5 kcal more per day (342.4 to 1284.7; P =.0041) compared with during the non‐UPF period. Regarding the chewing frequency, the number of chews per calorie was significantly lower during the UPF period (P =.016). Conclusions: Consumption of UPFs causes significant weight gain. Medical nutritional therapy focused on reducing the consumption of UPFs could be an effective strategy for preventing obesity. [ABSTRACT FROM AUTHOR]

A study published in the journal Diabetes, Obesity & Metabolism examined the effects of semaglutide injections on treatment satisfaction and eating behavior in Japanese patients with type 2 diabetes mellitus (T2DM). The study found that semaglutide injections increased treatment satisfaction and improved eating behavior in patients with T2DM, particularly those with obesity. The injections also resulted in decreased body weight and HbA1c levels in both groups. However, adverse events were reported, with loss of appetite being the most frequent. The study suggests that semaglutide injections may be a beneficial treatment option for Japanese patients with T2DM and obesity, but further research is needed to confirm these findings. [Extracted from the article]

Aim: To investigate the effects of once‐daily oral semaglutide 50 mg on energy intake, appetite, control of eating and gastric emptying. Methods: A clinical pharmacology, double‐blind study was conducted in 61 adults with obesity randomized to once‐daily oral semaglutide (dose‐escalated to 50 mg) or placebo for 20 weeks. Energy intake was measured during an ad libitum lunch, and participant‐reported appetite ratings and Control of Eating Questionnaire responses were assessed. Gastric emptying was measured using paracetamol absorption following a standardized breakfast. Results: The relative change from baseline in ad libitum energy intake at week 20 (primary endpoint) was −39.2% points (95% confidence interval −59.0%, −19.4%) with semaglutide compared with placebo. Body weight was reduced by 9.8% with semaglutide and by 1.5% with placebo. Semaglutide reduced hunger, increased fullness and satiety, and was associated with fewer food cravings and better control of eating versus placebo. No statistically significant difference in gastric emptying was observed at week 20. Conclusions: In participants with obesity, once‐daily oral semaglutide 50 mg reduced energy intake, body weight and appetite, and improved control of eating. There was no evidence of delayed gastric emptying at week 20, as measured through paracetamol absorption. [ABSTRACT FROM AUTHOR]

A study published in the journal Diabetes, Obesity & Metabolism examined the effects of a weight-loss program combined with respiratory muscle training (RMT) on weight and cardiovascular risk in adults with obesity. The study found that participants who followed the program experienced significant improvements in weight management and biomarkers, such as blood pressure and blood glucose levels. Compliance with the program was linked to positive outcomes. The study suggests that a combination of portion control and RMT could be an effective approach for weight loss and improving cardiovascular health in individuals with obesity. However, the study had limitations, including a small sample size and lack of a control group. [Extracted from the article]

Background: Childhood obesity is a crucial public health issue. Early childhood is a critical time to foster the establishment of healthy eating behaviours and growth, which are partly shaped by parental feeding practices. To inform French parents of the recently updated national complementary feeding guidelines for 0–3 years (in terms of nutrition and responsive feeding as a mean to encourage infant appetite control skills and promote healthy growth), an official printed brochure was developed and nationally disseminated in 2021 by the French public health agency, Santé publique France. This randomised controlled trial aims to investigate whether the provision of guidelines through digital (smartphone application) and printed (brochure) tools (vs. the printed brochure alone, usual service) results in healthier parental feeding practices, infant eating behaviours and weight status. Methods: This double-blinded monocentric 2-arm trial is currently conducted among first-time parents living in the area of Dijon (France) and recruited in a maternity ward. From child age 3 to 36 months (mo), an app provides a range of 106 age-adapted messages, including dietary recommendations, educational advice, recipes, and tips (intervention group only). Additionally, parents of both groups are provided with 48 messages related to child general development and the printed brochure at child age 2.7 mo. The primary outcome is the body mass index (BMI) z-score at child age 36 mo. Secondary outcome measures include a combination of online parents' reports and behavioural assessments (experimental meals) of parental feeding practices and infant eating behaviours from inclusion to 36 months of age. Analyses of covariance on these outcomes will assess the effect of the intervention, adjusted for relevant confounders. Complementary mediation and moderation analyses will be conducted. Sample size was determined to be n = 118 in each arm of the trial, plus 20% to compensate for potential attrition. Discussion: This is the first public eHealth randomised control trial in France to assess the effect of a web-based and mobile intervention targeted to first-time parents to improve child feeding practices and child growth. Trial registration: This trial was registered at clinicaltrials.gov as NCT05285761 (March 18, 2022). [ABSTRACT FROM AUTHOR]

Summary This systematic review and meta‐analysis synthesized evidence pertaining to consummatory and appetitive responses to acute exercise in children and adolescents with and without obesity (5–18 years). Articles reporting on supervised, controlled trials of any modality, duration, or intensity with laboratory‐measured food intake were found using MEDLINE, EMBASE, and Cochrane up to July 2023. Differences between conditions in laboratory energy and macronutrient intake, appetite sensations, and food reward were quantitatively synthesized using random‐effects meta‐analyses. Thirty‐five studies were eligible for the systematic review of energy intake, consisting of 60 distinct intervention arms with lean (n = 374) and overweight/obesity participants (n = 325; k = 51 eligible for meta‐analysis). Study quality as indicated by the Effective Public Healthy Practice Project tool was rated as low and moderate risk of bias for 80% and 20% of studies, respectively. Acute exercise had no significant effect on energy intake during an ad libitum test meal (mean difference [MD] = −4.52 [−30.58, 21.54] kcal, p = .729). Whilst absolute carbohydrate intake was lower after exercise (23 arms; MD = −6.08 [−11.26, −0.91] g, p = .023), the proportion of carbohydrate was not (30 arms; MD = −0.62 [−3.36, 2.12] %, p = .647). A small elevation in hunger (27 arms; MD = 4.56 [0.75, 8.37] mm, p = .021) and prospective food consumption (27 arms; PFC; MD = 5.71 [1.62, 9.80] mm, p = .008) was observed post‐exercise, but not immediately prior to the test meal (Interval: Mdn = 30 min, Range = 0–180). Conversely, a modest decrease in explicit wanting for high‐fat foods was evident after exercise (10 arms; MD = −2.22 [−3.96, −0.47] mm, p = .019). Exercise intensity (p = .033) and duration (p = .013) moderated food intake only in youth with overweight/obesity, indicating lower intake at high intensity and short duration. Overall, acute exercise does not lead to compensation of energy intake or a meaningful elevation of appetite or food reward and might have a modest benefit in youth with overweight/obesity if sufficiently intense. However, conclusions are limited by substantial methodological heterogeneity and the small number of trials employing high‐intensity exercise, especially in youth with overweight/obesity. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS), which can be induced or exacerbated by the current class of antipsychotic drugs, is highly prevalent in patients with schizophrenia and presents significant challenges to lifetime disease management. Supported by initial clinical results, trace amine‐associated receptor 1 (TAAR1) agonists have emerged as potential novel treatments for schizophrenia. Notably, non‐clinical studies have also shown weight‐lowering and glucoregulatory effects of TAAR1 agonists, including the investigational agent ulotaront. However, the translatability of these findings to humans has not been adequately assessed. Given that delayed gastric emptying (GE) was identified as a potential mechanism contributing to the metabolic benefits of TAAR1 agonists in rodents, the aim of this study was to evaluate the effect of ulotaront on GE in patients with schizophrenia and concurrent MetS with prediabetes. Methods: Patients with schizophrenia were randomized to receive a single oral dose of ulotaront (150 mg) and their previous antipsychotic (PA) in an open‐label, crossover, two‐sequence design (NCT05402111). Eligible participants fulfilled at least three of five MetS criteria and had prediabetes defined by elevated glycated haemoglobin (5.7‐6.4%) and/or fasting homeostatic model assessment of insulin resistance (i.e. ≥2.22). Following an overnight fast and 4 h post‐dose, participants ingested a 99mTc‐sulphur colloid radiolabelled egg meal (320 kcal, 30% fat). GE was measured by scintigraphy over 4 h. Endpoints included GE of solids half‐time (T1/2) and percentage gastric retention at 1, 2 and 4 h. Results: Thirty‐one adults were randomized and 27 completed the study. Ulotaront significantly delayed GE of solids [median GE T1/2 ulotaront at 139 min (119, 182) vs. the participant's PA of 124 min (109, 132), p =.006]. A significant increase in gastric retention was seen in the ulotaront versus the PA group at 1 h (80% vs. 75%, p =.015), 2 h (61% vs. 50%, p =.023) and 4 h (17% vs. 7%, p =.002) post‐meal. Conclusion: Ulotaront delayed the GE of solids in patients with schizophrenia and concurrent MetS with prediabetes. Additional studies are needed to assess whether treatment with TAAR1 agonists is associated with weight loss and glucoregulatory improvement. [ABSTRACT FROM AUTHOR]

DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) is produced by multiple cell types and detectable in blood plasma. DBI acts on GABRA (gamma-aminobutyric acid type A receptor) complexes containing GABRG2 (gamma-aminobutyric acid type A receptor, subunit gamma 2) to inhibit macroautophagy/autophagy and hence can be considered as an “autophagy checkpoint”. In patients with poor-prognosis anorexia nervosa, as well as in mice developing stress-induced anorexia, circulating DBI levels are reduced. Using a chemical-genetic system that makes it possible to control DBI secretion by hepatocytes, we showed that increasing DBI levels suffices to prevent anorexia induced by chronic restraint stress or chemotherapy with cisplatin, doxorubicin or paclitaxel in mice. At the mechanistic level, DBI administration acts through GABRA outside of the central nervous system and reduces the plasma levels of anorexigenic factors such as GDF15 (growth differentiation factor 15) and LCN2 (lipocalin 2), as well as anorexigenic signaling via the LCN2 receptor MC4R (melanocortin 4 receptor) in the hypothalamus. Accordingly, DBI supplementation stimulates food intake and normalizes whole body weight, body composition and metabolism in mouse models of anorexia. This normalization extends to the liver transcriptome and metabolome. Altogether, it appears that enhancing DBI levels constitutes a promising strategy for combating anorexia. [ABSTRACT FROM AUTHOR]

Over the past few decades, there has been a global surge in the prevalence of obesity, rendering it a globally recognized epidemic. Contrary to simply being a medical condition, obesity is an intricate disease with a multifactorial aetiology. Understanding the precise cause of obesity remains a challenge; nevertheless, there seems to be a complex interplay among biological, psychosocial and behavioural factors. Studies on the genetic factors of obesity have revealed several pathways in the brain that play a crucial role in food intake regulation. The best characterized pathway, thus far, is the leptin–melanocortin pathway, from which disruptions are responsible for the majority of monogenic obesity disorders. The effectiveness of conservative lifestyle interventions in addressing monogenic obesity has been limited. Therefore, it is crucial to complement the management strategy with pharmacological and surgical options. Emphasis has been placed on developing drugs aimed at replacing the absent signals, with the goal of restoring the pathway. In both monogenic and polygenic forms of obesity, outcomes differ across various interventions, likely due to the multifaceted nature of the disease. This underscores the need to explore alternative therapeutic strategies that can mitigate this heterogeneity. Precision medicine can be regarded as a powerful tool that can address this concern, as it values the understanding of the underlying abnormality triggering the disease and provides a tailored treatment accordingly. This would assist in optimizing outcomes of the current therapeutic approaches and even aid in the development of novel treatments capable of more effectively managing the global obesity epidemic. [ABSTRACT FROM AUTHOR]

Bardet‐Biedl syndrome (BBS) is a genetic disorder characterized by early‐onset obesity, polydactyly, genital and kidney anomalies, developmental delay and vision loss due to rod‐cone dystrophy. BBS is an autosomal recessive disorder with >20 implicated genes. The genotype–phenotype relationship in BBS is not clear, and there may be additional modifying factors. The underlying mechanism is dysfunction of primary cilia. In BBS, receptor trafficking in and out of the cilia is compromised, affecting multiple organ systems. Along with early‐onset obesity, hyperphagia is a prominent symptom and contributes significantly to clinical morbidity and caregiver burden. While there is no cure for BBS, setmelanotide is a new pharmacotherapy approved for treatment of obesity in BBS. The differential diagnosis for BBS includes other ciliopathies, such as Alstrom syndrome, and other genetic obesity syndromes, such as Prader‐Willi syndrome. Careful clinical history and genetic testing can help determine the diagnosis and a multidisciplinary team is necessary to guide clinical management. [ABSTRACT FROM AUTHOR]

Bardet‐Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as well as metabolic dysfunction, including obesity and an increased risk of type 2 diabetes. It is a primary ciliopathy, and causative mutations in more than 25 different genes have been described. Multiple cellular mechanisms contribute to the development of the metabolic phenotype associated with BBS, including hyperphagia as a consequence of altered hypothalamic appetite signalling as well as alterations in adipocyte biology promoting adipocyte proliferation and adipogenesis. Within this review, we describe in detail the metabolic phenotype associated with BBS and discuss the mechanisms that drive its evolution. In addition, we review current approaches to the metabolic management of patients with BBS, including the use of weight loss medications and bariatric surgery. Finally, we evaluate the potential of targeting hypothalamic appetite signalling to limit hyperphagia and induce clinically significant weight loss. [ABSTRACT FROM AUTHOR]

Background: Hypothalamic centres have been recognized to play a central role in body weight regulation for nearly 70 years. Aims: In this review, we will explore the current undersanding of the role the hypothalamus plays in controlling food intake behaviours. Materials and Methods: Review of relevant literature from PubMed searches and review article citations. Results: Beginning with autopsy studies showing destructive hypothalamic lesions in patients manifesting hyperphagia and rapid weight gain, followed by animal lesioning studies pinpointing adjacent hypothalamic sites as the 'satiety' centre and the 'feeding' centre of the brain, the neurocircuitry that governs our body weight is now understood to consist of a complex, interconnected network, including the hypothalamus and extending to cortical sites, reward centres and brainstem. Neurons in these sites receive afferent signals from the gastrointestinal tract and adipose tissue indicating food availability, calorie content, as well as body fat mass. Discussion: Integration of these complex signals leads to modulation of the two prime effector systems that defend a body fat mass set point: food intake and energy expenditure. Conclusion: Understanding the hypothalamic control of food intake forms the foundation for understanding and managing obesity as a chronic disease. [ABSTRACT FROM AUTHOR]

Obesity is a debilitating disease of global proportions that necessitates refined, concept‐driven therapeutic approaches. Policy makers, the public and even health care professionals, but also individuals with obesity harbour many misconceptions regarding this disease, which leads to prejudice, negative attitudes, stigmatization, discrimination, self‐blame, and failure to provide and finance adequate medical care. Decades of intensive, successful scientific research on obesity have only had a very limited effect on this predicament. We propose a science‐based, easy‐to‐understand conceptual model that synthesizes the complex pathogenesis of obesity including biological, psychological, social, economic and environmental aspects with the aim to explain and communicate better the nature of obesity and currently available therapeutic modalities. According to our integrative 'Behavioral Balance Model', 'top‐down cognitive control' strategies are implemented (often with limited success) to counterbalance the increased 'bottom‐up drive' to gain weight, which is triggered by biological, psycho‐social and environmental mechanisms in people with obesity. Besides offering a deeper understanding of obesity, the model also highlights why there is a strong need for multimodal therapeutic approaches that may not only increase top‐down control but also reduce a pathologically increased bottom‐up drive. [ABSTRACT FROM AUTHOR]

Aim: This study assessed the impact of dapagliflozin on food intake, eating behaviour, energy expenditure, magnetic resonance imaging (MRI)‐determined brain response to food cues and body composition in patients with type 2 diabetes mellitus (T2D). Materials and Methods: Patients were given dapagliflozin 10 mg once daily in a randomized, double‐blind, placebo‐controlled trial with short‐term (1 week) and long‐term (12 weeks) cross‐over periods. The primary outcome was the difference in test meal food intake between long‐term dapagliflozin and placebo treatment. Secondary outcomes included short‐term differences in test meal food intake, short‐ and long‐term differences in appetite and eating rate, energy expenditure and functional MRI brain activity in relation to food images. We determined differences in glycated haemoglobin, weight, liver fat (by 1H magnetic resonance spectroscopy) and subcutaneous/visceral adipose tissue volumes (by MRI). Results: In total, 52 patients (43% were women) were randomized; with the analysis of 49 patients: median age 58 years, weight 99.1 kg, body mass index 35 kg/m2, glycated haemoglobin 49 mmol/mol. Dapagliflozin reduced glycated haemoglobin by 9.7 mmol/mol [95% confidence interval (CI) 3.91‐16.27, p =.004], and body weight (−2.84 vs. −0.87 kg) versus placebo. There was no short‐ or long‐term difference in test meal food intake between dapagliflozin and placebo [mean difference 5.7 g (95% CI −127.9 to 139.3, p =.933); 15.8 g (95% CI −147.7 to 116.1, p =.813), respectively] nor in the rate of eating, energy expenditure, appetite, or brain responses to food cues. Liver fat (median reduction −4.7 vs. 1.95%), but not subcutaneous/visceral adipose tissue, decreased significantly with 12 weeks of dapagliflozin. Conclusions: The reduction in body weight and liver fat with dapagliflozin was not associated with compensatory adaptations in food intake or energy expenditure. [ABSTRACT FROM AUTHOR]

A high consumption of ultra-processed food (UPF) is a hallmark of Western diets that has been related to increased risk of non-communicable diseases. As an underlying mechanism, UPF may promote non-alcoholic fatty liver disease (NAFLD) which is a key driver of metabolic impairment with extra-hepatic manifestations like type 2 diabetes, cardiovascular disease, chronic kidney disease, and osteoporosis among others. The present review provides an overview of UPF properties that may promote NAFLD and are thus potential targets for reformulation of UPF. Such approaches should address improvements in the quality of carbohydrates and fat, changes in food texture that lower eating rate as well as ingredients that prevent excess caloric intake or avoid dysbiosis and leaky gut syndrome. Promising strategies are enrichment with fiber, prebiotics, phytochemicals, and protein with a concurrent reduction in glycemic load, energy density, saturated fatty acids (FA; SFA), emulsifiers, fructose, and non-caloric sweeteners. Future studies are needed to examine the interactive and protective effects of such modifications in the composition of UPF on prevention and treatment of NAFLD.

Adiponectin (AdipoQ) is an adipokine involved in glucose homeostasis and lipid metabolism. In mammals, its role in appetite control is highly controversial. To shed light on the comparative aspects of AdipoQ in lower vertebrates, goldfish was used as a model to study feeding regulation by AdipoQ in fish species. As a first step, goldfish AdipoQ was cloned and found to be ubiquitously expressed at the tissue level. Using sequence alignment, protein modeling, phylogenetic analysis and comparative synteny, goldfish AdipoQ was shown to be evolutionarily related to its fish counterparts and structurally comparable with AdipoQ in higher vertebrates. In our study, recombinant goldfish AdipoQ was expressed in E. coli, purified by IMAC, and confirmed to be bioactive via activation of AdipoQ receptors expressed in HepG2 cells. Feeding in goldfish revealed that plasma levels of AdipoQ and its transcript expression in the liver and brain areas involved in appetite control including the telencephalon, optic tectum, and hypothalamus could be elevated by food intake. In parallel studies, IP and ICV injection of recombinant goldfish AdipoQ in goldfish was effective in reducing foraging behaviors and food consumption. Meanwhile, transcript expression of orexigenic factors (NPY, AgRP, orexin, and apelin) was suppressed with parallel rises in anorexigenic factors (POMC, CART, CCK, and MCH) in the telencephalon, optic tectum and/or hypothalamus. In these brain areas, transcript signals for leptin receptor were upregulated with concurrent drops in the NPY receptor and ghrelin receptors. In the experiment with IP injection of AdipoQ, transcript expression of leptin was also elevated with a parallel drop in ghrelin mRNA in the liver. These findings suggest that AdipoQ can act as a novel satiety factor in goldfish. In this case, AdipoQ signals (both central and peripheral) can be induced by feeding and act within the brain to inhibit feeding behaviors and food intake via differential regulation of orexigenic/anorexigenic factors and their receptors. The feeding inhibition observed may also involve the hepatic action of AdipoQ by modulation of feeding regulators expressed in the liver. [ABSTRACT FROM AUTHOR]

Aim: Weight bias, stigma and discrimination are pervasive in the health care system and society and may result in biased treatment of people living with obesity (PwO). We aimed to identify perceptions, attitudes and potential barriers that exist between people with obesity and health care professionals (HCPs) in Denmark. Methods: The ACTION‐DK survey was a cross‐sectional, non‐interventional, descriptive study conducted in Denmark. The cohort included 879 PwO (body mass index ≥30.0 kg/m2) based on self‐reported height and body weight, and 100 HCPs from the primary and secondary sectors who frequently encountered PwO. Results: Several discrepancies between PwO and HCPs were identified, including recognition of obesity as a chronic disease (PwO: 49% vs. HCPs: 84%) and whether PwO were responsible for their weight loss (PwO: 81% vs. HCPs: 17%). Among PwO, 46% were motivated to lose weight, but only 28% of HCPs shared this perception. Untimely initiation of obesity care consultations was also identified as a potential barrier to proper obesity care, as PwO waited 7 years, on average, from their initial decision to lose weight before having their first obesity care consultation. In addition, only 24% of PwO had a follow‐up consultation after the initial obesity care discussion. Almost half of HCPs (46%) considered weight loss medication effective, but only 10% brought up this possibility during an obesity care discussion. Conclusions: Our findings suggest that it is pivotal to improve obesity care in Denmark by ensuring a better follow‐up and alignment of the perceptions and attitudes toward obesity between PwO and HCPs. [ABSTRACT FROM AUTHOR]

Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor which has been defined mostly as a regulator of the appetite/hunger balance mechanisms to date. In addition to its function regarding the weight gain and appetite control mechanisms of MC3R, recent studies have shown that MC3R controls growth, puberty, and circadian rhythms as well. Despite the drastic effects of MC3R deficiency in humans and other mammals, its cellular mechanisms are still under investigation. In this review paper, we aimed to point out the importance of MC3R regulations in three main areas: 1) its impact on weight and appetite control, 2) its role in the control of growth, puberty, and the circadian rhythm, and, 3) its protein-protein interactions and cellular mechanisms.

Based on our previous work, in which acute intravenous hormone infusion reduced food intake in healthy men,[11] a sample size of 16 people would have 90% power (at a significance level of 0.05) to detect a clinically significant reduction in food intake of 2.3 ± 1.3 kcal/kg. This is the first study to report on the effect of kisspeptin on appetite, food intake, glucose and insulin levels in women, and in people who are overweight or have obesity. Keywords: appetite control; experimental pharmacology; randomized trial; weight control EN appetite control experimental pharmacology randomized trial weight control 2393 2397 5 07/04/23 20230801 NES 230801 BACKGROUND Kisspeptin is recognized to have a critical role in the control of reproductive function[[1]]; however, as reproductive processes require adequate energy stores, there is increasing focus on its interaction with metabolic processes. (B) Luteinizing hormone (LH) levels were higher during kisspeptin infusion compared with vehicle infusion (**p < .01). gl Serum insulin, plasma glucose, serum luteinizing hormone (LH) and serum oestradiol were measured in the Clinical Chemistry Laboratory of Imperial College Healthcare NHS Trust. [Extracted from the article]

CCK as brain-gut peptide, binds to its receptor (CCKR) and participates in physiological processes such as feeding and digestion in animals. In order to study the function of CCKs and CCKRs in largemouth bass (Micropterus salmoides) in feeding activities, the coding sequences of CCK1, CCK2, CCK1R and CCK2R were cloned in this study. Their lengths were 414, 387, 1368 and 1359 bp, and their encodes were 137, 128, 455 and 452 amino acids, respectively. Fluorescence quantitative results showed that both CCK1 and CCK2 were highly expressed in brain, followed by intestinal, while CCK1R and CCK2R were highly expressed in gallbladder and brain, respectively. Within 24h after ingestion, the relative expressions of CCK1, CCK2, CCK1R and CCK2R increased first and then decreased. The relative expression of CCK1, CCK1R and CCK2R reached the highest value at 3h after ingestion, while the relative expression of CCK2 was at 12h after ingestion. The relative expression reached the highest value (P<0.05). During fasting, the relative expression of CCK1, CCK1R and CCK2R was significantly increased on the 14th day of fasting (P<0.05). The relative expression trends of CCK1, CCK1R and CCK2R after refeeding were similar to those after meals, showing a trend of first increasing and then decreasing. However, there was no significant change in the relative expression of CCK2 during fasting and refeeding. In conclusion, the results of this study indicated that CCK1 can be combined with CCK1R and CCK2R to act as a satiety signal factor to regulate physiological processes such as feeding and digestion of largemouth bass by suppressing appetite; CCK2 may act as a short-term appetite factor to regulate feeding. Activity. The results of this study can provide a theoretical basis for the regulation of feeding activities of largemouth bass. [ABSTRACT FROM AUTHOR]

Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor which has been defined mostly as a regulator of the appetite/hunger balance mechanisms to date. In addition to its function regarding the weight gain and appetite control mechanisms of MC3R, recent studies have shown that MC3R controls growth, puberty, and circadian rhythms as well. Despite the drastic effects of MC3R deficiency in humans and other mammals, its cellular mechanisms are still under investigation. In this review paper, we aimed to point out the importance of MC3R regulations in three main areas: 1) its impact on weight and appetite control, 2) its role in the control of growth, puberty, and the circadian rhythm, and, 3) its protein-protein interactions and cellular mechanisms. [ABSTRACT FROM AUTHOR]

This study determines obestatin-like substances from the young shoots of the tea plant [Camellia sinensis (L.) O. Kuntze (Theaceae)]. Proteins were extracted from the vegetative tea leaves using the QB (Quick Buffer) buffer as an extraction buffer. Obestatin-like substances in tea extract were investigated using an indirect home-made enzyme-linked immunosorbent assay (ELISA). Human obestatin-like immunoreactive substances from tea extract were isolated and characterized by tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (tricine-SDS-PAGE) and immunoblotting techniques. Immunochemical results showed that there are strong human obestatin-like immunoreactive substances (0.048 ± 0.0064 ng/mg protein) in vegetative tea leaves. This finding was completely unexpected since this hormone was considered to be present solely in animals. Furthermore, a single obestatin-like immunoreactive protein band of 13 kDa was identified by tricine-SDS-PAGE and Western blotting of extract of vegetative tea leaf proteins. Present investigation is the first report of presence of obestatin-like immunoreactive substances in plants. It is concluded that obestatin-like bioactive peptides derived from plants can affect gastrointestinal tract structures as endogenous obestatin does and hence play a role in appetite regulation and body weight gain. [ABSTRACT FROM AUTHOR]

Background: Appetite represents a desire of a person to eat specific food in order to reach satisfaction and pleasure states. This desire may be associated with the experience of negative or positive emotions (emotional appetite). Emotional appetite can influence eating behavior, and its investigation is relevant to avoid possible damage to health resulting from a disordered eating. Objectives: To adapt the Emotional Appetite Questionnaire (EMAQ) to the Portuguese language; to assess the validity and reliability of the data; and to assess emotional appetite in three samples of adults collected before and after the outbreak of the COVID-19 pandemic. Methods: This is a cross-sectional study with non-probabilistic convenience sampling. The Portuguese version of the EMAQ was presented after translation, back-translation, and content analysis. Two studies were conducted, the first before and the second after the pandemic onset. Three samples were formed (2019: Sample 1 (age = 19.7 ± 1.5 years) n = 323; 2020: Sample 2 (age = 21.3 ± 1.8 years) n = 1,011; and Sample 3 (age = 28.9 ± 3.1 years) n = 909). An exploratory strategy with parallel analysis was performed. The analyses were conducted in FACTOR and R (lavaan and semTools packages) software. After determining the best-fit model for the data, emotional appetite was examined considering decrease, non-alteration, and increase in appetite in the face of positive and negative emotions/situations. The profile of emotional appetite was determined using a circumplex model. Results: The two-factor model described by the valence of emotions/situations fitted the samples (Comparative Fit Indexminimum-maximum = 0.95-0.98; Tucker-Lewis Index = 0.94-0.98; Root Mean Square Error of Approximation = 0.03-0.08; aord = 0.78-0.88). Increases in appetite were more frequent for positive emotions/situations (52.0-57.5%), and both decreases (35.4-44.5%) and increases (50.0-56.2%) in appetite were observed for negative emotions/situations. Emotions with negative valence and activation were more relevant to appetite reduction, while a significant increase in appetite was observed with anxiety (negative valence and positive activation). Conclusion: Different emotions and situations may influence appetite in people, and such an investigation may be useful in preparing eating protocols. [ABSTRACT FROM AUTHOR]

Background Appetite represents a desire of a person to eat specific food in order to reach satisfaction and pleasure states. This desire may be associated with the experience of negative or positive emotions (emotional appetite). Emotional appetite can influence eating behavior, and its investigation is relevant to avoid possible damage to health resulting from a disordered eating. Objectives To adapt the Emotional Appetite Questionnaire (EMAQ) to the Portuguese language; to assess the validity and reliability of the data; and to assess emotional appetite in three samples of adults collected before and after the outbreak of the COVID-19 pandemic. Methods This is a cross-sectional study with non-probabilistic convenience sampling. The Portuguese version of the EMAQ was presented after translation, back-translation, and content analysis. Two studies were conducted, the first before and the second after the pandemic onset. Three samples were formed (2019: Sample 1 (age = 19.7 ± 1.5 years) n = 323; 2020: Sample 2 (age = 21.3 ± 1.8 years) n = 1,011; and Sample 3 (age = 28.9 ± 3.1 years) n = 909). An exploratory strategy with parallel analysis was performed. The analyses were conducted in FACTOR and R (lavaan and semTools packages) software. After determining the best-fit model for the data, emotional appetite was examined considering decrease, non-alteration, and increase in appetite in the face of positive and negative emotions/situations. The profile of emotional appetite was determined using a circumplex model. Results The two-factor model described by the valence of emotions/situations fitted the samples (Comparative Fit Indexminimum-maximum = 0.95–0.98; Tucker-Lewis Index = 0.94–0.98; Root Mean Square Error of Approximation = 0.03–0.08; αord = 0.78–0.88). Increases in appetite were more frequent for positive emotions/situations (52.0–57.5%), and both decreases (35.4–44.5%) and increases (50.0–56.2%) in appetite were observed for negative emotions/situations. Emotions with negative valence and activation were more relevant to appetite reduction, while a significant increase in appetite was observed with anxiety (negative valence and positive activation). Conclusion Different emotions and situations may influence appetite in people, and such an investigation may be useful in preparing eating protocols.

With the rising prevalence of global obesity, development of satiety-enhancing and satiation-enhancing food model is always a focus in weight management. Food-related behavioral studies are focused on food choice, eating practices and food consumption to effectively control appetite by regulating energy and food intake. Thus, enhancing the satiating power of the food through food matrix modification could be situated within the food behaviour context. To date, the existing satiety- and satiation-enhancing food model is often based on the role of food composition. Common practices such as reducing the consumption of high-sugar, high-calorie and energy-dense foods, while increasing the consumption of fruits and vegetables have always been encouraged to prevent obesity. The modification of food structure could be a new approach to affect food-related behavior as well as eating habits by way of enhancing satiety and satiation. However, recent reviews regarding the satiety- or satiation-based approaches are mainly found within the context of western countries. Thus, it is important to study the current challenges in combating the problem of overweight and obesity, especially in the Asian region. In this article, relationships between food consumption, changes of food behaviour in terms of food matrix modification as well as satiety and satiation of consumer are studied further for verification using the social behavioural laboratory at the Centre for Human Excellence and Development as outlined in reference to appetite control. [ABSTRACT FROM AUTHOR]

AimsThere are no treatments for the extreme hyperphagia and obesity in Prader-Willi syndrome (PWS). The bestPWS clinical trial assessed the efficacy, safety and tolerability of the methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib.Materials and methodsParticipants with PWS (12-65 years old) were randomly assigned (1:1:1) to biweekly placebo, 1.8 mg beloranib or 2.4 mg beloranib injection for 26 weeks at 15 US sites. Co-primary endpoints were the changes in hyperphagia [measured by Hyperphagia Questionnaire for Clinical Trials (HQ-CT); possible score 0-36] and weight by intention-to-treat. ClinicalTrials.gov registration: NCT02179151.ResultsOne-hundred and seven participants were included in the intention-to-treat analysis: placebo (n = 34); 1.8 mg beloranib (n = 36); or 2.4 mg beloranib (n = 37). Improvement (reduction) in HQ-CT total score was greater in the 1.8 mg (mean difference -6.3, 95% CI -9.6 to -3.0; P = .0003) and 2.4 mg beloranib groups (-7.0, 95% CI -10.5 to -3.6; P = .0001) vs placebo. Compared with placebo, weight change was greater with 1.8 mg (mean difference - 8.2%, 95% CI -10.8 to -5.6; P < .0001) and 2.4 mg beloranib (-9.5%, 95% CI -12.1 to -6.8; P < .0001). Injection site bruising was the most frequent adverse event with beloranib. Dosing was stopped early due to an imbalance in venous thrombotic events in beloranib-treated participants (2 fatal events of pulmonary embolism and 2 events of deep vein thrombosis) compared with placebo.ConclusionsMetAP2 inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia-related behaviours and weight loss in participants with PWS. Although investigation of beloranib has ceased, inhibition of MetAP2 is a novel mechanism for treating hyperphagia and obesity.

Martínez-Gómez, MG and Roberts, BM. Metabolic adaptations to weight loss: A brief review. J Strength Cond Res 36(10): 2970–2981, 2022—As the scientific literature has continuously shown, body mass loss attempts do not always follow a linear fashion nor always go as expected even when the intervention is calculated with precise tools. One of the main reasons why this tends to happen relies on our body's biological drive to regain the body mass we lose to survive. This phenomenon has been referred to as "metabolic adaptation" many times in the literature and plays a very relevant role in the management of obesity and human weight loss. This review will provide insights into some of the theoretical models for the etiology of metabolic adaptation as well as a quick look into the physiological and endocrine mechanisms that underlie it. Nutritional strategies and dietetic tools are thus necessary to confront these so-called adaptations to body mass loss. Among some of these strategies, we can highlight increasing protein needs, opting for high-fiber foods or programming-controlled diet refeeds, and diet breaks over a large body mass loss phase. Outside the nutritional aspects, it might be wise to increase the physical activity and thus the energy flux of an individual when possible to maintain diet-induced body mass loss in the long term. This review will examine these protocols and their viability in the context of adherence and sustainability for the individual toward successful body mass loss. [ABSTRACT FROM AUTHOR]

We investigated the effects of complex textural attributes of food i.e. lubricity and oral coating, on appetite ratings, food intake, salivary and gut peptides for the first time. Milk protein-rich beverages (whey and casein) were instrumentally analyzed (tribology, viscosity and adsorption, latter representing oral coating) using in vitro measurements. Then these protein beverage preloads differing in their coating properties (low coating, medium coating and high coating) were assessed in two cross-over satiety trials (Study 1, n=37; Study 2, n=15; Total n= 52). Fullness ratings increased in the high coating beverage condition (p < .05) only after 20 min with limited effects on other time points, suggesting a sporadic effect of oral coating on appetite ratings (n=37). There was a correlation between concentration of protein in saliva and appetite ratings; the higher the concentration of protein in saliva the lower the desire to eat (r = - 0.963; p < 0.05) and prospective food consumption ratings (r =- 0.980; p < 0.05). Human saliva was more lubricating after ingesting preload with high coating properties, thus explaining the results on appetite ratings. There was no effect of oral coating on energy intake and gut peptides (n=15), suggesting that complex textural attributes having influence on oral processing might not have any effect on the later parts of the satiety cascade. Oral coating/ lubricity appears to have a subtle and sporadic effect on appetite suppression, which needs further investigation with changing macronutrients/energy load and degree of coating/ lubricity., Competing Interests: Declaration of competing interest There are no known conflicts of interest associated with this publication., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To evaluate whether the potent hypophagic and weight‐suppressive effects of growth differentiation factor‐15 (GDF15) and semaglutide combined would be a more efficacious antiobesity treatment than either treatment alone by examining whether the neural and behavioural mechanisms contributing to their anorectic effects were common or disparate. Materials/Methods: Three mechanisms were investigated to determine how GDF15 and semaglutide induce anorexia: the potentiation of the intake suppression by gastrointestinal satiation signals; the reduction in motivation to feed; and the induction of visceral malaise. We then compared the effects of short‐term, combined GDF15 and semaglutide treatment on weight loss to the individual treatments. Rat pharmaco‐behavioural experiments assessed whether GDF15 or semaglutide added to the satiating effects of orally gavaged food and exogenous cholecystokinin (CCK). A progressive ratio operant paradigm was used to examine whether GDF15 or semaglutide reduced feeding motivation. Pica behaviour (ie, kaolin intake) and conditioned affective food aversion testing were used to evaluate visceral malaise. Additionally, fibre photometry studies were conducted in agouti‐related protein (AgRP)‐Cre mice to examine whether GDF15 or semaglutide, alone or in combination with CCK, modulate calcium signalling in hypothalamic AgRP neurons. Results: Semaglutide reduced food intake by amplifying the feeding‐inhibitory effect of CCK or ingested food, inhibited the activity of AgRP neurons when combined with CCK, reduced feeding motivation and induced malaise. GDF15 induced visceral malaise but, strikingly, did not affect feeding motivation, the satiating effect of ingested food or CCK signal processing. Combined GDF15 and semaglutide treatment produced greater food intake and body weight suppression than did either treatment alone, without enhancing malaise. Conclusions: GDF15 and semaglutide reduce food intake and body weight through largely distinct processes that produce greater weight loss and feeding suppression when combined. [ABSTRACT FROM AUTHOR]

To explore the feeding regulatory mechanism of the leptin gene and its receptor, the full‐length cDNA of Tbleptin‐B and TbleptinR were cloned from Trachinotus blochii, and their expression patterns in different dietary strategies were analysed. The preprandial expressions of Tbleptin‐A, Tbleptin‐B and TbleptinR in liver showed a downward trend as a function of time. However, 1 h after postprandial, Tbleptin‐A increased significantly, Tbleptin‐B decreased significantly, TbleptinR did not change, and their postprandial expressions were not significantly different with the control group at 3 h. This result indicated that Tbleptin‐A and Tbleptin‐B were involved in the postprandial regulation of liver within 3 h. Similarly, the expressions of Tbleptin‐A, Tbleptin‐B and TbleptinR in liver were not different from the control group after refeeding (d11), which showed that the expressions of them in liver would return to normal level after long‐term hungry golden pomfret getting enough food. In hypothalamus, the postprandial expressions of Tbleptin‐B and TbleptinR were significantly increased at 1 h, while Tbleptin‐A was inhibited. Similarly, after refeeding, the expression of Tbleptin‐A was significantly lower than that of the control group, and Tbleptin‐B was significantly higher than that of the control group. In summary, Tbleptin‐A, Tbleptin‐B and TbleptinR play different roles in coping with different dietary strategies in liver and hypothalamus. Tbleptin‐A is mainly involved in dietary regulation through liver, while Tbleptin‐B and TbleptinR are mainly active in the hypothalamus. These results provide valuable information to reveal the T. blochii feeding regulatory mechanism. [ABSTRACT FROM AUTHOR]

Restoring the control of food intake is the key to obesity management and prevention. The arcuate nucleus (ARC) of the hypothalamus is extensively being studied as a potential anti-obesity target. Animal studies showed that neuropeptide FF (NPFF) reduces food intake by its action in neuropeptide Y (NPY) neurons of the hypothalamic ARC, but the detailed mode of action observed in human neurons is missing, due to the lack of a human-neuron-based model for pharmacology testing. Here, we validated and utilized a human-neural-stem-cell-based (hNSC) model of ARC to test the effects of NPFF on cellular pathways and neuronal activity. We found that in the human neurons, decreased cAMP levels by NPFF resulted in a reduced rate of cytoplasmic calcium oscillations, indicating an inhibition of ARC NPY neurons. This suggests the therapeutic potential of NPFFR2 in obesity. In addition, we demonstrate the use of human-stem-cell-derived neurons in pharmacological applications and the potential of this model to address functional aspects of human hypothalamic neurons. [ABSTRACT FROM AUTHOR]

The human circadian system consists of the master clock in the suprachiasmatic nuclei of the hypothalamus as well as in peripheral molecular clocks located in organs throughout the body. This system plays a major role in the temporal organization of biological and physiological processes, such as body temperature, blood pressure, hormone secretion, gene expression, and immune functions, which all manifest consistent diurnal patterns. Many facets of modern life, such as work schedules, travel, and social activities, can lead to sleep/wake and eating schedules that are misaligned relative to the biological clock. This misalignment can disrupt and impair physiological and psychological parameters that may ultimately put people at higher risk for chronic diseases like cancer, cardiovascular disease, and other metabolic disorders. Understanding the mechanisms that regulate sleep circadian rhythms may ultimately lead to insights on behavioral interventions that can lower the risk of these diseases. On February 25, 2021, experts in sleep, circadian rhythms, and chronobiology met virtually for the Keystone eSymposium "Sleep & Circadian Rhythms: Pillars of Health" to discuss the latest research for understanding the bidirectional relationships between sleep, circadian rhythms, and health and disease. [ABSTRACT FROM AUTHOR]

Antipsychotic drugs (APDs) represent a cornerstone in the treatment of schizophrenia and other psychoses. The effectiveness of the first generation (typical) APDs are hampered by so-called extrapyramidal side effects, and they have gradually been replaced by second (atypical) and third-generation APDs, with less extrapyramidal side effects and, in some cases, improved efficacy. However, the use of many of the current APDs has been limited due to their propensity to stimulate appetite, weight gain, and increased risk for developing type 2 diabetes and cardiovascular disease in this patient group. The mechanisms behind the appetite-stimulating effects of the various APDs are not fully elucidated, partly because their diverse receptor binding profiles may affect different downstream pathways. It is critical to identify the molecular mechanisms underlying drug-induced hyperphagia, both because this may lead to the development of new APDs, with lower appetite-stimulating effects but also because such insight may provide new knowledge about appetite regulation in general. Hence, in this review, we discuss the receptor binding profile of various APDs in relation to the potential mechanisms by which they affect appetite.

Neuropsychiatric disorders (NPDs) are a huge burden to the patient, their family, and society. NPDs have been greatly associated with cardio-metabolic comorbidities such as obesity, type-2 diabetes mellitus, dysglycaemia, insulin resistance, dyslipidemia, atherosclerosis, and other cardiovascular disorders. Antipsychotics, which are frontline drugs in the treatment of schizophrenia and off-label use in other NPDs, also add to this burden by causing severe metabolic perturbations. Despite decades of research, the mechanism deciphering the link between neuropsychiatric and metabolic disorders is still unclear. In recent years, transient receptor potential Ankyrin 1 (TRPA1) channel has emerged as a potential therapeutic target for modulators. TRPA1 agonists/antagonists have shown efficacy in both neuropsychiatric disorders and appetite regulation and thus provide a crucial link between both. TRPA1 channels are activated by compounds such as cinnamaldehyde, allyl isothiocyanate, allicin and methyl syringate, which are present naturally in food items such as cinnamon, wasabi, mustard, garlic, etc. As these are present in many daily food items, it could also improve patient compliance and reduce the patients' monetary burden. In this review, we have tried to present evidence of the possible involvement of TRPA1 channels in neuropsychiatric and metabolic disorders and a possible hint towards using TRPA1 modulators to target appetite, lipid metabolism, glucose and insulin homeostasis and inflammation associated with NPDs. [ABSTRACT FROM AUTHOR]

Aim: To clarify the distinct effects of a long‐acting (liraglutide) and a short‐acting (lixisenatide) glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) on macronutrient intake, gastrointestinal side effects and pancreas function. Materials and Methods: Fifty participants were randomized to either lixisenatide or liraglutide for a treatment period of 10 weeks. Appetite, satiety, macronutrient intake, gastrointestinal symptoms and variables related to pancreatic function and gastric emptying were assessed at baseline and after treatment. Results: Both GLP‐1 RAs reduced macronutrient intake similarly. Weight loss and appetite reduction were not related to the delay in gastric emptying or gastrointestinal side effects (P >.05). Lipase increased significantly with liraglutide treatment (by 18.3 ± 4.1 U/L; P =.0001), but not with lixisenatide (−1.8 ± 2.4 U/L; P =.46). Faecal elastase and serum ß‐carotin levels (indicators for exocrine pancreas function) improved in both groups (P <.05). Changes in lipase activities did not correlate with gastrointestinal symptoms (P >.05 for each variable). Conclusions: Both GLP‐1 RAs comparably affected body weight, energy and macronutrient intake. Both treatments were associated with indicators of improved exocrine pancreas function. Reductions in appetite and body weight as a result of treatment with short‐ or long‐acting GLP‐1 RAs are not driven by changes in gastric emptying or gastrointestinal side effects. [ABSTRACT FROM AUTHOR]

Aim: To compare a Mediterranean diet (MED) with a high‐fibre vegetarian diet (HFV) in terms of hunger‐satiety perception through post‐prandial assessment of appetite‐related hormones glucagon‐like peptide 1 (GLP‐1) and oxyntomodulin, as well as self‐rated visual analogue scale (VAS) quantification, in overweight/obese subjects with type 2 diabetes (T2D). Materials and methods: Twelve T2D subjects (Male to female ratio = 7:5), mean age 63 ± 8.5 years, were enrolled in a randomized, controlled, crossover study. Participants consumed an MED meal as well as an isocaloric meal rich in complex carbohydrate as well as an isocaloric MED meal in two different visits with a 1‐week washout period between the two visits. Appetite ratings, glucose/insulin, and gastrointestinal hormone concentrations were measured at fasting and every 30' until 210' following meal consumption. Results: GLP‐1 and oxyntomodulin levels were significantly higher following MED meal compared with HFV meals (210' area under the curve, p < 0.022 and p < 0.023, respectively). Both MED and HFV meal resulted in a biphasic pattern of GLP‐1 and oxyntomodulin, although MED meal was related to a delayed, significantly higher second GLP‐1 peak at 150' compared with that of HFV meal (p < 0.05). MED meal was related to lower glucose profile compared with HFV meal (p < 0.039), whereas we did not observe significant changes in terms of self‐reported VAS scores and insulin trend. Conclusions: In T2D overweight/obese subjects, an MED meal is more effective than a HFV meal in terms of post‐prandial plasma glucose homoeostasis and GLP‐1 and oxyntomodulin release. These changes were not confirmed by VAS appetite self‐assessment over a 210' period. [ABSTRACT FROM AUTHOR]

Neuropsychiatric disorders (NPDs) are a huge burden to the patient, their family, and society. NPDs have been greatly associated with cardio-metabolic comorbidities such as obesity, type-2 diabetes mellitus, dysglycaemia, insulin resistance, dyslipidemia, atherosclerosis, and other cardiovascular disorders. Antipsychotics, which are frontline drugs in the treatment of schizophrenia and off-label use in other NPDs, also add to this burden by causing severe metabolic perturbations. Despite decades of research, the mechanism deciphering the link between neuropsychiatric and metabolic disorders is still unclear. In recent years, transient receptor potential Ankyrin 1 (TRPA1) channel has emerged as a potential therapeutic target for modulators. TRPA1 agonists/antagonists have shown efficacy in both neuropsychiatric disorders and appetite regulation and thus provide a crucial link between both. TRPA1 channels are activated by compounds such as cinnamaldehyde, allyl isothiocyanate, allicin and methyl syringate, which are present naturally in food items such as cinnamon, wasabi, mustard, garlic, etc. As these are present in many daily food items, it could also improve patient compliance and reduce the patients’ monetary burden. In this review, we have tried to present evidence of the possible involvement of TRPA1 channels in neuropsychiatric and metabolic disorders and a possible hint towards using TRPA1 modulators to target appetite, lipid metabolism, glucose and insulin homeostasis and inflammation associated with NPDs.

GNPDA2 has been associated with human obesity and type-2 diabetes by using a GWAS approach. GNPDA2 is an enzyme involved in the hexosamine biosynthesis pathway, which is known to be important for nutrient sensing in various organism. Its counter enzyme, GFAT, has previously been shown to be important to the development of insulin resistance in diabetes. The implication of GNPDA2 and GFAT in metabolism is scarce and the effect of both enzymes over appetite and glucose homeostasis is unknown.Aim: Identify the role of GNPDA2 and GFAT in nutrient sensing circuits of the CNS that are important for the regulation of both appetite and glucose homeostasis.Methods: Using Long Evans rats, we administered either a GNPDA2 or GFAT antagonist or vehicle in i3vt.Key Findings:GNPDA2 is highly expressed in hypothalamus and adipose tissue, followed by muscle and liver. GNPDA2 is expressed in different hypothalamic nuclei (ARC, DMH, LHA, PVN). GNPDA2 is downregulated in hypothalamus under diet-induced obesity (as previously described), but GFAT expression does not change. Moreover, i3vt infusion of GNPDA2 or GFAT inhibitor resulted in increased c-Fos in areas related to appetite and glucose homeostasis control as PVN and DMH and to a lesser extent in the LHA and ARC. Central inhibition of GNPDA2 does not alter either acute food intake or body weight; however, GFAT inhibition diminished appetite and body weight due to visceral illness. In addition, central administration of the GNPDA2 antagonist, prior to an intraperitoneal glucose tolerance test, resulted in glucose intolerance in comparison to vehicle without altering insulin levels.Significance: These results suggest that central GNPDA2 does not control appetite, but regulates glucose homeostasis.

Neuropeptide Y (NPY) is known as a potent orexigenic signal in vertebrates, but its role in Atlantic salmon has not yet been fully established. In this study, we identified three npy paralogs, named npya1, npya2, and npyb, in the Atlantic salmon genome. In silico analysis revealed that these genes are well conserved across the vertebrate’s lineage and the mature peptide sequences shared at least 77% of identity with the human homolog. We analyzed mRNA expression of npy paralogs in eight brain regions of Atlantic salmon post-smolt, and the effect of 4 days of fasting on the npy expression level. Results show that npya1 was the most abundant paralog, and was predominantly expressed in the telencephalon, followed by the midbrain and olfactory bulb. npya2 mRNA was highly abundant in hypothalamus and midbrain, while npyb was found to be highest expressed in the telencephalon, with low mRNA expression levels detected in all the other brain regions. 4 days of fasting resulted in a significant (p < 0.05) decrease of npya1 mRNA expression in the olfactory bulb, increased npya2 mRNA expression in the midbrain and decreased npyb mRNA expression in the pituitary. In the hypothalamus, the vertebrate appetite center, expression of the npy paralogs was not significantly affected by feeding status. However, we observed a trend of increased npya2 mRNA expression (p = 0.099) following 4 days of fasting. Altogether, our findings provide a solid basis for further research on appetite and energy metabolism in Atlantic salmon.

Spexin (SPX) is a pleiotropic peptide with highly conserved protein sequence from fish to mammals and its biological actions are mediated by GalR2/GalR3 receptors expressed in target tissues. Recently, SPX has been confirmed to be a novel satiety factor in fish species but whether the peptide has a similar function in mammals is still unclear. Using the mouse as a model, the functional role of SPX in feeding control and the mechanisms involved were investigated. After food intake, serum SPX in mice could be up-regulated with elevations of transcript expression and tissue content of SPX in the glandular stomach but not in other tissues examined. As revealed by immunohistochemical staining, food intake also intensified SPX signals in the major cell types forming the gastric glands (including the foveolar cells, parietal cells, and chief cells) within the gastric mucosa of glandular stomach. Furthermore, IP injection of SPX was effective in reducing food intake with parallel attenuation in transcript expression of NPY, AgRP, NPY type 5 receptor (NPY5R), and ghrelin receptor (GHSR) in the hypothalamus, and these inhibitory effects could be blocked by GalR3 but not GalR2 antagonism. In agreement with the central actions of SPX, similar inhibition on feeding and hypothalamic expression of NPY, AgRP, NPY5R, and GHSR could also be noted with ICV injection of SPX. In the same study, in contrast to the drop in NPY5R and GHSR, SPX treatment could induce parallel rises of transcript expression of leptin receptor (LepR) and melanocortin 4 receptor (MC4R) in the hypothalamus. These findings, as a whole, suggest that the role of SPX as a satiety factor is well conserved in the mouse. Apparently, food intake can induce SPX production in glandular stomach and contribute to the postprandial rise of SPX in circulation. Through GalR3 activation, this SPX signal can act within the hypothalamus to trigger feedback inhibition on feeding by differential modulation of feeding regulators (NPY and AgRP) and their receptors (NPY5R, GHSR, LepR, and MC4R) involved in the feeding circuitry within the CNS.

In mammals, time-restricted feeding (TRF) with no caloric restriction provides health benefits and extends longevity, usually with a minor (∼3%) or no reduction in total food consumption. In the current study, a TRF regimen of 6 h free access to food (08:00–14:00 h) was applied to Leghorn chickens from 25 to 86 weeks of age; control birds ate freely during the light hours (06:00–20:00 h). Unexpectedly, the TRF-treated birds consumed, on average, 11.7% less food than the controls. This was manifested by an average reduction of 9.6% in body weight, 2.6-fold in visceral fat accumulation, and 6.5% in egg weight. Hen-housed egg production was reduced by 3.6% in the TRF group compared with the control, along the first 40 weeks of the follow-up (P < 0.05), and changed into a tendency of 0.7% higher egg production thereafter. Several parameters of egg quality showed significant improvement (P < 0.05) in the TRF group compared with the controls. A comparison of diurnal patterns of feed consumption revealed a higher rate of hourly consumption in the TRF group and increased consumption before dark in the control group. In conclusion, the reduced feed intake in response to the TRF treatment and loss in visceral fat accumulation supports the lack of a strong adipostat activity in chickens and different appetite regulation mechanisms compared with mammals. Therefore, future TRF studies in chickens should be adjusted by extending the ad libitum time window. The lower feed intake by the TRF-treated chickens compared with the ad libitum-fed controls seems to reduce the efficiency of egg production. Nevertheless, the improved egg quality and persistence of egg lay at the older age suggest that similarly to mammals, the TRF treatment delayed at least some of the negative impacts associated with advanced age.

Background: A phase 2 trial has suggested that treatment with the melanocortin-4 receptor (MC4R) agonist setmelanotide is associated with a decrease in hunger and weight-related outcomes in participants with Bardet-Biedl syndrome (BBS) and Alström syndrome. Here, we present the study design of an ongoing, randomized, double-blind, placebo-controlled, phase 3 trial to assess the long-term efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in individuals with BBS or Alström syndrome (ClinicalTrials.gov identifier: NCT03746522). Methods: It was initially planned that ~30 participants aged ≥6 years with a clinical diagnosis of BBS or Alström syndrome would be enrolled. Participants with obesity as defined by a body mass index ≥30 kg/m2 (in those aged ≥16 years) or a weight >97th percentile (in those aged 6–15 years) are included. Participants are initially randomized in a 1:1 ratio to receive setmelanotide or placebo for 14 weeks (period 1). Following period 1, all participants receive 38 weeks of open-label treatment with setmelanotide (period 2). In each treatment period, setmelanotide is administered at 3 mg once a day following completion of dose escalation. The primary endpoint is the proportion of participants aged ≥12 years achieving a clinically meaningful reduction from baseline (≥10%) in body weight after ~52 weeks (eg, following period 2). Safety and tolerability are assessed by frequency of adverse events. Conclusions: This pivotal trial is designed to evaluate the efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in individuals with BBS and Alström syndrome. Submission category: Study Design, Statistical Design, Study Protocols.

Neuropeptide Y (NPY) is known as a potent orexigenic signal in vertebrates, but its role in Atlantic salmon has not yet been fully established. In this study, we identified three npy paralogs, named npya1, npya2, and npyb , in the Atlantic salmon genome. In silico analysis revealed that these genes are well conserved across the vertebrate's lineage and the mature peptide sequences shared at least 77% of identity with the human homolog. We analyzed mRNA expression of npy paralogs in eight brain regions of Atlantic salmon post-smolt, and the effect of 4 days of fasting on the npy expression level. Results show that npya1 was the most abundant paralog, and was predominantly expressed in the telencephalon, followed by the midbrain and olfactory bulb. npya2 mRNA was highly abundant in hypothalamus and midbrain, while npyb was found to be highest expressed in the telencephalon, with low mRNA expression levels detected in all the other brain regions. 4 days of fasting resulted in a significant (p < 0.05) decrease of npya1 mRNA expression in the olfactory bulb, increased npya2 mRNA expression in the midbrain and decreased npyb mRNA expression in the pituitary. In the hypothalamus, the vertebrate appetite center, expression of the npy paralogs was not significantly affected by feeding status. However, we observed a trend of increased npya2 mRNA expression (p = 0.099) following 4 days of fasting. Altogether, our findings provide a solid basis for further research on appetite and energy metabolism in Atlantic salmon. [ABSTRACT FROM AUTHOR]