Search

Context Ghrelin circulates in acylated (AG) and deacylated (DAG) forms, which are known to affect appetite. Although acute exercise has been shown to modulate ghrelin levels, data on the impact of exercise intensity on AG and DAG levels and their effects on appetite are sparse and primarily limited to males. Objective To investigate the effect of exercise intensity and sex on ghrelin levels and appetite in untrained humans. Methods Eight males (age: 43.1 ± 10.9 years; body mass index [BMI]: 22.2 ± 1.7 kg/m2; peak oxygen consumption [VO2peak]: 36.3 ± 6.4 mL/kg/min) and 6 females (age: 32.2 ± 11.1 years; BMI: 22.7 ± 1.0 kg/m2; VO2peak: 29.2 ± 4.0 mL/kg/min) completed a maximal graded cycle ergometer lactate threshold (LT)/VO2peak test. These data were used to determine the exercise intensity on 3 subsequent randomized control or calorically matched cycle exercise bouts: (1) CON, no exercise; (2) MOD, the power output at LT; (3) HIGH, the power output associated with 75% of the difference between LT and VO2peak. Perception of appetite was analyzed using visual analog scales. Results Females had higher levels of total ghrelin (TG) (P =.03) and DAG (P =.01) at baseline than males. Both groups exhibited reduced DAG levels in HIGH compared with MOD and CON (P <.0001-.004); however, only females had significantly reduced AG in HIGH (P <.0001). Hunger scores were higher in MOD than in CON (P <.01). Conclusion High-intensity may be superior to moderate-intensity exercise for reducing ghrelin levels and modifying hunger, and sex may impact this response. [ABSTRACT FROM AUTHOR]

Background/Objective: Obesity, clinically defined as a body mass index (BMI) of 30 kg/m2 or higher, is a medical condition characterized by the excessive accumulation of body fat, which can lead to adverse health consequences. As a global public health issue with an escalating prevalence, controlling appetite and satiety is essential for regulating energy balance and managing body weight. Dietary proteins and peptides have gained interest in their potential to prevent and treat obesity by modulating satiety signals. This narrative review analyzes scientific evidence highlighting the role of dietary proteins and peptides in regulating satiety signals and investigates their therapeutic potential in preventing and treating obesity. Methods: A comprehensive literature search was conducted in multiple electronic databases, including PubMed, Scopus, and Web of Science. The search focused on articles examining the impact of dietary proteins and peptides on satiety and obesity, encompassing both preclinical and clinical trials. Results: Several studies have demonstrated a correlation between the intake of specific proteins or peptides from plant and animal sources and satiety regulation. These investigations identified mechanisms where amino acids and peptides interact with enteroendocrine cell receptors, activating intracellular signaling cascades that promote the release of anorexigenic gut hormones such as cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). Both in vitro and in vivo assays have shown that these interactions contribute to appetite regulation and the sensation of satiety. Conclusions: Using proteins and peptides in the diet may be an effective strategy for regulating appetite and controlling body weight. However, more research—including clinical trials—is needed to understand the underlying mechanisms better and optimize the application of these bioactive compounds in preventing and treating obesity. [ABSTRACT FROM AUTHOR]

The first systematic reviews of the effects of exercise on appetite‐regulation and energy intake demonstrated changes in appetite‐regulating hormones consistent with appetite suppression and decreases in subsequent relative energy intake over a decade ago. More recently, an intensity‐dependent effect and several potential mechanisms were proposed, and this review aims to highlight advances in this field. While exercise‐induced appetite suppression clearly involves acylated ghrelin, glucagon‐like peptide‐1 may also be involved, though recent evidence suggests peptide tyrosine tyrosine may not be relevant. Changes in subjective appetite perceptions and energy intake continue to be equivocal, though these results are likely due to small sample sizes and methodological inconsistencies. Of the proposed mechanisms responsible for exercise‐induced appetite suppression, lactate has garnered the most support through in vitro and in vivo rodent studies as well as a growing amount of work in humans. Other potential modulators of exercise‐induced appetite suppression may include sex hormones, growth‐differentiation factor 15, Lac‐Phe, brain‐derived neurotrophic factor, and asprosin. Research should focus on the mechanisms responsible for the changes and consider these other modulators (i.e., myokines/exerkines) of appetite to improve our understanding of the role of exercise on appetite regulation. [ABSTRACT FROM AUTHOR]

Purpose: To determine the relationship between gastrointestinal hormones (leptin, glucagon-like peptide-1), ghrelin, cholecystokinin, peptide YY, morphological characteristics, and physical performances in elite soccer players. Methods: Q2 Twenty-two elite male soccer players (age = 23.1 [2.7] y, height = 177.0 [0.1] cm, weight = 70.2 [2.9] kg, body mass index = 22.1 [1.8] kg/m2) completed 3-day food records each week during the 5-week training period. Blood samples were drawn after an overnight fast before and after preseason training to assess gastrointestinal hormones (leptin, glucagon-like peptide-1, ghrelin, cholecystokinin, and peptide YY). Continuous analysis of the training load was used during the training period. Preintervention and postintervention tests assessed jumping (countermovement jump), sprinting (10, 20, and 30 m), and endurance fitness (the Yo-Yo Intermittent Recovery Test Level 1 [YYIRT1]) levels. Results: Preseason training decreased body mass index (P =.001; effect size [ES] = 0.183) and body fat percentage (P =.001; ES = 0.516). There were increases in countermovement jump (P =.032; ES = 0.215), 20- (P =.016; ES = 0.195) and 30-m sprints (P =.001; ES = 0.188), and YYIRT1 performance (P =.001; ES = 0.9). Levels of cholecystokinin, peptide YY, and ghrelin did not change during preseason training, although changes in leptin (P =.001; ES = 0.41) and glucagon-like peptide-1 levels (P =.039; ES = 0.606) were recorded. Leptinemia correlated with anthropometric parameters (body mass index, r =.77, P =.001; percentage of body fat,r =.67, P =.006) and the total distance covered during the YYIRT1 (r = −.54; P =.03). Conclusion: Changes in morphological parameters and physical performance in elite-level male soccer players are related to variations in selected gastrointestinal hormones. [ABSTRACT FROM AUTHOR]

Late chronotype (LC) is related to obesity and altered food intake throughout the day. But whether appetite perception and gut hormones differ among chronotypes is unclear. Thus, we examined if early chronotype (EC) have different appetite responses in relation to food intake than LC. Adults with obesity were categorized using the Morningness-Eveningness Questionnaire (MEQ) as either EC (n = 21, 18F, MEQ = 63.9 ± 1.0, 53.7 ± 1.2 yr, 36.2 ± 1.1 kg/m2) and LC (n = 28, 24F, MEQ = 47.2 ± 1.5, 55.7 ± 1.4 yr, 37.1 ± 1.0 kg/m2). Visual analog scales were used during a 120 min 75 g oral glucose tolerance test (OGTT) at 30 min intervals to assess appetite perception, as well as glucose, insulin, GLP-1 (glucagon-like polypeptide-1), GIP (glucose-dependent insulinotrophic peptide), PYY (protein tyrosine tyrosine), and acylated ghrelin. Dietary intake (food logs), resting metabolic rate (RMR; indirect calorimetry), aerobic fitness (maximal oxygen consumption (VO2max)), and body composition dual-energy X-ray absorptiometry (DXA) were also assessed. Age, body composition, RMR, and fasting appetite were similar between groups. However, EC had higher satisfaction and fullness as well as reduced desires for sweet, salty, savory, and fatty foods during the OGTT (P<0.05). Only GIP tAUC0–120 min was elevated in EC versus LC (p = 0.01). Daily dietary intake was similar between groups, but EC ate fewer carbohydrates (p = 0.05) and more protein (p = 0.01) at lunch. Further, EC had lower caloric (p = 0.03), protein (p = 0.03) and fat (p = 0.04) intake during afternoon snacking compared to LC. Dietary fat was lower, and carbohydrates was higher, in EC than LC (p = 0.05) at dinner. Low glucose and high insulin as well as GLP-1 tAUC60–120 min related to desires for sweet foods (p < 0.05). Taken together, EC had more favorable appetite and lower caloric intake later in the day compared with LC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract The first systematic reviews of the effects of exercise on appetite‐regulation and energy intake demonstrated changes in appetite‐regulating hormones consistent with appetite suppression and decreases in subsequent relative energy intake over a decade ago. More recently, an intensity‐dependent effect and several potential mechanisms were proposed, and this review aims to highlight advances in this field. While exercise‐induced appetite suppression clearly involves acylated ghrelin, glucagon‐like peptide‐1 may also be involved, though recent evidence suggests peptide tyrosine tyrosine may not be relevant. Changes in subjective appetite perceptions and energy intake continue to be equivocal, though these results are likely due to small sample sizes and methodological inconsistencies. Of the proposed mechanisms responsible for exercise‐induced appetite suppression, lactate has garnered the most support through in vitro and in vivo rodent studies as well as a growing amount of work in humans. Other potential modulators of exercise‐induced appetite suppression may include sex hormones, growth‐differentiation factor 15, Lac‐Phe, brain‐derived neurotrophic factor, and asprosin. Research should focus on the mechanisms responsible for the changes and consider these other modulators (i.e., myokines/exerkines) of appetite to improve our understanding of the role of exercise on appetite regulation.

Excess adiposity can contribute to metabolic complications, such as type 2 diabetes mellitus (T2DM), which poses a significant global health burden. Traditionally viewed as a chronic and irreversible condition, T2DM management has evolved and new approaches emphasizing reversal and remission are emerging. Bariatric surgery demonstrates significant improvements in body weight and glucose homeostasis. However, its complexity limits widespread implementation as a population-wide intervention. The identification of glucagon-like peptide 1 (GLP-1) and the development of GLP-1 receptor agonists (GLP-1RAs) have improved T2DM management and offer promising outcomes in terms of weight loss. Innovative treatment approaches combining GLP-1RA with other gut and pancreatic-derived hormone receptor agonists, such as glucose-dependant insulinotropic peptide (GIP) and glucagon (GCG) receptor agonists, or coadministered with amylin analogues, are demonstrating enhanced efficacy in both weight loss and glycemic control. This review aims to explore the benefits of bariatric surgery and emerging pharmacological therapies such as GLP-1RAs, and dual and triple agonists in managing obesity and T2DM while highlighting the caveats and evolving landscape of treatment options.

Objective: The effect of oral glucose-induced release of gastrointestinal hormones on satiety and appetite independently of prevailing plasma glucose excursions is unknown. The objective is to investigate the effect of oral glucose on appetite and satiety sensations as compared to isoglycemic IV glucose infusion (IIGI) in healthy volunteers. Design: A crossover study involving two study days for each participant. Participants: Nineteen healthy participants (6 women, mean age 55.1 [SD 14.2] years; mean body mass index 26.7 [SD 2.2] kg/m²). Interventions: Each participant underwent a 3-h 50-g oral glucose tolerance test (OGTT) and, on a subsequent study day, an IIGI mimicking the glucose excursions from the OGTT. On both study days, appetite and satiety were indicated regularly on visual analog scale (VAS), and blood was drawn regularly for measurement of pancreatic and gut hormones. Primary outcomes: Difference in appetite and satiety sensations during OGTT and IIGI. Results: Circulating concentrations of glucose-dependent insulinotropic polypeptide (P < .0001), glucagon-like peptide 1 (P < .0001), insulin (P < .0001), C-peptide (P < .0001), and neurotensin (P = .003) increased significantly during the OGTT as compared to the IIGI, whereas glucagon responses were similarly suppressed (P = .991). Visual analog scale-assessed ratings of hunger, satiety, fullness, thirst, well-being, and nausea, respectively, were similar during OGTT and IIGI whether assessed as mean 0-3-h values or area under the curves. For both groups, a similar, slow increase in appetite and decrease in satiation were observed. Area under the curve, for prospective food consumption (P = .049) and overall appetite score (P = .044) were slightly lower during OGTT compared to IIGI, whereas mean 0-3-h values were statistically similar for prospective food consumption (P = .053) and overall appetite score (P = .063). Conclusions: Despite eliciting robust responses of appetite-reducing and/or satiety-promoting gut hormones, we found that oral glucose administration has little or no effect on appetite and satiety as compared to an IIGI, not affecting the release of appetite-modulating hormones. Trial registry no: ClinicalTrials.gov: NCT01492283 and NCT06064084. [ABSTRACT FROM AUTHOR]

Aims: Alongside its metabolic implications, obesity and associated diabetes impair female reproductive function, causing infertility and polycystic ovarian syndrome (PCOS). Recently, gut hormones and their receptors have been identified in various reproductive organs indicating their potential regulatory effects on reproductive function. This review aims to give an overview of their potential effects. Methods: This review focuses on literature that outlines modifications during obesity, diabetes and related infertility with an emphasis on gut hormones and their therapeutic potential. Results: Evidence suggests that bariatric surgery has positive effects on fertility and PCOS where major alterations in metabolism occurs through restoration of gut hormone levels. This is thought to be due to the indirect effect weight loss and regulation of blood glucose has on the hypothalamic–pituitary–ovarian and hypothalamic–pituitary–adrenal axis influencing reproduction. Conclusions: Further research is required to elucidate the cellular mechanisms involved in the direct effects of gut hormone receptor activation on reproductive tissues. Current observations suggest a therapeutic role for gut hormones in infertility/PCOS associated with metabolic pathophysiology. [ABSTRACT FROM AUTHOR]

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.

Emma Custers,&ast; Ayla Franco,&ast; Amanda Johanne Kiliaan Department of Medical Imaging, Anatomy, Radboud University Medical Center, Donders Institute for Brain Cognition and Behaviour, Nijmegen, the Netherlands&ast;These authors contributed equally to this workCorrespondence: Amanda Johanne Kiliaan, Department of Medical Imaging, Anatomy, Preclinical Imaging Centre, Radboud Alzheimer Center, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Geert Grooteplein 21N, Nijmegen, 6525 EZ, the Netherlands, Tel +31 24 3614378, Email Amanda.Kiliaan@Radboudumc.nlAbstract: Obesity is associated with systemic inflammation, comorbidities like diabetes, cardiovascular disease and several cancers, cognitive decline and structural and functional brain changes. To treat, or potentially prevent these related comorbidities, individuals with obesity must achieve long-term sustainable weight loss. Often life style interventions, such as dieting and increased physical activity are not successful in achieving long-term weight loss. Meanwhile bariatric surgery has emerged as a safe and effective procedure to treat obesity. Bariatric surgery causes changes in physiological processes, but it is still not fully understood which exact mechanisms are involved. The successful weight loss after bariatric surgery might depend on changes in various energy regulating hormones, such as ghrelin, glucagon-like peptide-1 and peptide YY. Moreover, changes in microbiota composition and white adipose tissue functionality might play a role. Here, we review the effect of obesity on neuroendocrine effects, microbiota composition and adipose tissue and how these may affect inflammation, brain structure and cognition. Finally, we will discuss how these obesity-related changes may improve after bariatric surgery.Keywords: obesity, cognitive impairment, inflammation, gut hormones, adipose tissue, bariatric surgery

Gut hormones are a large class of polypeptides an. amines secreted by enteroendocrine cells (EECs), which play an important role in appetite regulation, gastrointestinal motility, digestive enzyme secretion, and blood pressure and glycemic control. The secretion of gut hormones is regulated by dietary factors, and food -derived bioactive peptides (FBPs are one of the important dietary factors regulating the secretion of gut hormones. This study reviewed the research progress and action mechanisms of FBPs regulating gut hormones secretion in recent years. In addition, the future research directions were prospected to provide reference for the research and application of FBPs in the regulation of gut hormones secretion. [ABSTRACT FROM AUTHOR]

Unhealthy diets rich in fats and/or sugar are considered as the major external cause of the obesity epidemic, which is often accompanied by a significant decrease in gut hormone glucagon-like peptide-1 (GLP1) levels. Numerous studies have demonstrated notable contributions of the gut microbiota in this process. Nevertheless, the underlying mechanism still needs further investigation. The role of epigenetic modifications in gene expression and metabolism has been well demonstrated, with m6A methylation on RNAs being the most prevalent modification throughout their metabolism. In the present study, we found that the expressions of small intestinal Gcg and Pc3, two key genes regulating GLP1 expression, were significantly downregulated in obese mice, associated with reduced GLP1 level. Immunohistochemistry analysis indicated that a high-fat diet slightly increased the density of enteroendocrine L cells in the small intestine, implying that decreased GLP1 levels were not caused by the changes in L cell intensity. Instead, the small intestinal m6A level as well as the expression of known "writers", mettl3/14 and wtap, were found to be positively correlated with the expression of Gcg and Pc3. Fecal microbiota transplantation with feces from normal and obese mice daily to antibiotic-treated mice revealed that dysbiosis in diet-induced obesity was sufficient to reduce serum GLP1, small intestinal m6A level, and intestinal expressions of Gcg, Pc3, and writer genes (mettl3/14, wtap). However, as the most direct and universal methyl donor, the production of fecal S-adenosylmethionine was neither affected by the different dietary patterns nor their shaped microbiota. These results suggested that microbial modulation of the epitranscriptome may be involved in regulating GLP1 expression, and highlighted epitranscriptomic modifications as an additional level of interaction between diet and individual health. [ABSTRACT FROM AUTHOR]

The current review examines the totality of the evidence to determine if there exists a relationship between β-glucan and body weight and adiposity and whether such a relationship is a consistent, causal and plausible one. Observational studies suggest an association between oat (i.e., β-glucan) intake and reduced body weight, waist circumference and adiposity. High and moderate quality randomized controlled trials that were specifically designed to evaluate the efficacy of β-glucan on anthropometric outcomes were given the highest weight. Several of these studies indicated a causal relationship between β-glucan consumption and reduction in body weight, BMi, and at least one measure of body fat within diets that were not calorie-restricted. A review of additional animal and human evidence suggests multiple plausible mechanisms by which β-glucan may impact satiety perception, gastric emptying, gut hormones, gut microbiota and short chain fatty acids in the complex interplay of appetite and energy regulation. [ABSTRACT FROM AUTHOR]

Obesity is a chronic disease associated with increased morbidity and mortality. Bariatric surgery can lead to sustained long-term weight loss (WL) and improvement in multiple obesity-related complications, but it is not scalable at the population level. Over the past few years, gut hormonebased pharmacotherapies for obesity and type 2 diabetes mellitus (T2DM) have rapidly evolved, and combinations of glucagon-like peptide 1 (GLP1) with other gut hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) as dual or triple agonists are under investigation to enhance and complement the effects of GLP1 on WL and obesity-related complications. Tirzepatide, a dual agonist of GLP1 and GIP receptors, marks a new era in obesity pharmacotherapy in which a combination of gut hormones could approach the WL achieved with bariatric surgery. In this review, we discuss emerging obesity treatments with a focus on gut hormone combinations and the concept of a multimodal approach for obesity management. [ABSTRACT FROM AUTHOR]

Abstract There are many trillions of bacteria in the gastrointestinal microbiome (GM). Their ecological dysregulation can contribute to the development of certain neurodegenerative diseases, including Alzheimer's disease (AD). AD is common dementia and its incidence is increasing year by year. However, the relationship between GM and AD is unclear. Therefore, this review discusses the relationship between GM and AD, elaborates on the possible factors that can affect this relationship through the inflammation of the brain induced by blood−brain damage and accumulation of amyloid deposit, and proposes feasible ways to treat AD through GM‐related substances, such as probiotics, Mega‐3, and gut hormones, including their shortcomings as well.

Short-chain fatty acids (SCFA) can regulate appetite by stimulating the secretion of satiety hormones. However, the impact of short-chain fatty acid propionate on the release of gut satiety hormones and appetite regulation in pigs is not completely understood. In this study, 16 pigs were infused with saline or sodium propionate through a fistula in the caecum during a 28-day experimental period. We characterized the effects of propionate administration on peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) secretion from colonic tissue, and investigated the role of propionate infusion on the expression of appetite-related genes in the colon and hypothalamus. Further, the direct impact of propionate administration on the expression of orexigenic neuropeptide agouti-related protein (AgRP) in hypothalamic N38 cells was also examined. The results showed that intra-cecal infusion of propionate reduced the short-term feed intake (P 0.05). Propionate administration stimulated PYY and GLP-1 release from colon tissue in vivo and ex vivo (P

Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality, and it is a major risk factor for the early onset of cardiovascular diseases (CVDs). More than genetics, food, physical activity, walkability, and air pollution are lifestyle factors, which have the greatest impact on T2DM. Certain diets have been shown to be associated with lower T2DM and cardiovascular risk. Diminishing added sugar and processed fats and increasing antioxidant-rich vegetable and fruit intake has often been highlighted, as in the Mediterranean diet. However, less is known about the interest of proteins in low-fat dairy and whey in particular, which have great potential to improve T2DM and could be used safely as a part of a multi-target strategy. This review discusses all the biochemical and clinical aspects of the benefits of high-quality whey, which is now considered a functional food, for prevention and improvement of T2DM and CVDs by insulin- and non-insulin-dependent mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: In patients with type 2 diabetes mellitus (T2DM), Roux-en-Y gastric bypass (RYGB) leads to beneficial metabolic adaptations, including enhanced incretin secretion, beta-cell function, and systemic insulin sensitivity. We explored the impact of RYGB on pituitary, pancreatic, gut hormones, and cortisol responses to parenteral and enteral nutrient stimulation in patients with obesity and T2DM with repeated sampling up to 2 years after intervention. Methods: We performed exploratory post hoc analyses in a previously reported randomized trial. Levels of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY), ACTH, insulin, and glucagon were measured in 13 patients with T2DM and obesity at four different visits: before and 4, 24, and 104 weeks after RYGB; and in three sequential conditions on the same day: fasting, intravenous arginine challenge, and OGTT. Results: RYGB surprisingly induced a rise in ACTH, cortisol, and GH levels upon an oral glucose load, together with enhanced GLP-1 and PYY responses. Fasting and post-arginine GH levels were higher after RYGB, whereas insulin, glucagon, GLP-1, GIP, and cortisol were lower. These endocrine adaptations were seen as early as 4 weeks after surgery and were maintained for up to 2 years. Conclusion: These findings indicate adaptations of glucose sensing mechanisms and responses in multiple endocrine organs after RYGB, involving the gut, pancreatic islets, the pituitary gland, the adrenals, and the brain.

Atherosclerotic cardiovascular disease is the most common cause of morbidity and mortality worldwide. Diabetes mellitus increases cardiovascular risk. Heart failure and atrial fibrillation are associated comorbidities that share the main cardiovascular risk factors. The use of incretin-based therapies promoted the idea that activation of alternative signaling pathways is effective in reducing the risk of atherosclerosis and heart failure. Gut-derived molecules, gut hormones, and gut microbiota metabolites showed both positive and detrimental effects in cardiometabolic disorders. Although inflammation plays a key role in cardiometabolic disorders, additional intracellular signaling pathways are involved and could explain the observed effects. Revealing the involved molecular mechanisms could provide novel therapeutic strategies and a better understanding of the relationship between the gut, metabolic syndrome, and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The brain, particularly the hypothalamus and brainstem, monitors and integrates circulating metabolic signals, including gut hormones. Gut–brain communication is also mediated by the vagus nerve, which transmits various gut-derived signals. Recent advances in our understanding of molecular gut–brain communication promote the development of next-generation anti-obesity medications that can safely achieve substantial and lasting weight loss comparable to metabolic surgery. Herein, we comprehensively review the current knowledge about the central regulation of energy homeostasis, gut hormones involved in the regulation of food intake, and clinical data on how these hormones have been applied to the development of anti-obesity drugs. Insight into and understanding of the gut–brain axis may provide new therapeutic perspectives for the treatment of obesity and diabetes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate associations of ghrelin, glucagon-like peptide 1 (GLP-1), and peptide YY 3–36 (PYY3-36) with weight change after bariatric arterial embolization (BAE). Materials and Methods: Subgroup analysis of data collected during the BEAT Obesity Trial involving 7 participants with BMI > 40 who were embolized with 300- to 500-μm Embosphere Microspheres. Three participants were characterized as "responders" (top tertile of weight loss at each visit) and 4 as "non-responders" (bottom tertile of weight loss at each visit). Mean ± standard deviation participant age was 44 ± 11 years, and 6 of 7 participants were women. Participants were evaluated at baseline, 2 weeks, and 1, 3, 6, and 12 months after BAE. After fasting, participants consumed a mixed meal test at each visit; blood samples were collected at 0, 15, 30, 60, 120, 180, and 240 min. Study outcome measures were changes in weight from baseline and plasma serum hormone levels. Results: Percentage change in ghrelin decreased significantly in non-responders at 60 and 120 min at 1 and 12 months (estimated difference between 60 vs. 0 min at 1 month: 69% [95% CI − 126%, − 13%]; estimated difference between 120 vs. 0 min at 12 months: − 131% (95% CI − 239%, − 23%]). Responders had significantly lower ghrelin and greater weight loss than non-responders at 6 and 12 months. GLP-1 and PYY3-36 levels did not differ between groups. Conclusion: Participants with consistent weight loss throughout follow-up had lower ghrelin than non-responders, supporting decreased ghrelin as a mechanism underlying BAE-induced weight loss. Level of Evidence I: High-quality randomized trial or prospective study; testing of previously developed diagnostic criteria on consecutive patients; sensible costs and alternatives; values obtained from many studies with multiway sensitivity analyses; systematic review of Level I RCTs and Level I studies. [ABSTRACT FROM AUTHOR]

The aim of this study was to perform a comprehensive literature review regarding the relevant hormonal and histologic changes observed after Roux-en-Y gastric bypass (RYGB). We aimed to describe the relevant hormonal (glucagon-like peptides 1 and 2 [GLP-1 and GLP-2], peptide YY [PYY], oxyntomodulin [OXM], bile acids [BA], cholecystokinin [CCK], ghrelin, glucagon, gastric inhibitory polypeptide [GIP], and amylin) profiles, as well as the histologic (mucosal cellular) adaptations happening after patients undergo RYGB. Our review compiles the current evidence and furthers the understanding of the rationale behind the food intake regulatory adaptations occurring after RYGB surgery. We identify gaps in the literature where the potential for future investigations and therapeutics may lie. We performed a comprehensive database search without language restrictions looking for RYGB bariatric surgery outcomes in patients with pre- and postoperative blood work hormonal profiling and/or gut mucosal biopsies. We gathered the relevant study results and describe them in this review. Where human findings were lacking, we included animal model studies. The amalgamation of physiologic, metabolic, and cellular adaptations following RYGB is yet to be fully characterized. This constitutes a fundamental aspiration for enhancing and individualizing obesity therapy. [ABSTRACT FROM AUTHOR]

Health claims on food labelling can influence peoples' perception of food without them actually eating it, for example driving a belief that a particular food will make them feel fuller. The aim of this study was to investigate whether nutrient and health claims on food labelling can influence self-reported, and physiological indicators of, satiation. A total of 50 participants attended two visits where they were asked to consume a 380 kcal breakfast (granola and yogurt) labelled as a 500 kcal 'indulgent' breakfast at one visit and as a 250 kcal 'sensible' breakfast at the other. The order of the breakfast descriptions was randomly allocated. Participants were unaware that the two breakfasts were the same product and that only the food labels differed. At each visit blood samples were collected to measure gut hormone levels (acylated ghrelin, peptide tyrosine-tyrosine and glucagon-like peptide-1) at three time points: 20 min after arrival (baseline), after 60 min (anticipatory, immediately prior to consumption) and after 90 min (post-consumption). Visual analogue scales measuring appetite (hunger, satiety, fullness, quantity and desire to eat) were completed prior to each sample. Between 60 and 90 min, participants consumed the breakfast and rated its sensory appeal. Participants reported a higher mean change in self-reported fullness for the 'indulgent' than the 'sensible' breakfast from anticipatory to post-consumption (mean difference: 7.19 [95% CI: 0.73, 13.6]; p = 0.030). This change was not observed for the other appetite measures at the other time points or gut hormone levels. This study suggests that nutrient and health claims on food labels may influence satiation as measured by self-reported fullness. It also suggests that the observed differences in satiety scores are not due to changes in the main appetite regulating gut hormones, but are more likely centrally mediated. More high-quality trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Gambling disorder (GD) is a modestly prevalent and severe condition for which neurobiology is not yet fully understood. Although alterations in signals involved in energy homeostasis have been studied in substance use disorders, they have yet to be examined in detail in GD. The aims of the present study were to compare different endocrine and neuropsychological factors between individuals with GD and healthy controls (HC) and to explore endocrine interactions with neuropsychological and clinical variables. A case–control design was performed in 297 individuals with GD and 41 individuals without (healthy controls; HCs), assessed through a semi-structured clinical interview and a psychometric battery. For the evaluation of endocrine and anthropometric variables, 38 HCs were added to the 41 HCs initially evaluated. Individuals with GD presented higher fasting plasma ghrelin (p < 0.001) and lower LEAP2 and adiponectin concentrations (p < 0.001) than HCs, after adjusting for body mass index (BMI). The GD group reported higher cognitive impairment regarding cognitive flexibility and decision-making strategies, a worse psychological state, higher impulsivity levels, and a more dysfunctional personality profile. Despite failing to find significant associations between endocrine factors and either neuropsychological or clinical aspects in the GD group, some impaired cognitive dimensions (i.e., WAIS Vocabulary test and WCST Perseverative errors) and lower LEAP2 concentrations statistically predicted GD presence. The findings from the present study suggest that distinctive neuropsychological and endocrine dysfunctions may operate in individuals with GD and predict GD presence. Further exploration of endophenotypic vulnerability pathways in GD appear warranted, especially with respect to etiological and therapeutic potentials. [ABSTRACT FROM AUTHOR]

Background: Weight loss can induce changes in appetite-regulating hormone levels, possibly linked to increases in appetite and weight regain. However, hormonal changes vary across interventions. Here, we studied levels of appetite-regulating hormones during a combined lifestyle intervention (CLI: healthy diet, exercise and cognitive behavioral therapy).Methods: We measured levels of long-term adiposity-related hormones (leptin, insulin, high-molecular-weight (HMW) adiponectin) and short-term appetite hormones (PYY, cholecystokinin, gastric-inhibitory polypeptide, pancreatic polypeptide, FGF21, AgRP) in overnight-fasted serum of 39 patients with obesity. Hormone levels were compared between T0 (baseline), T1 (after 10 weeks) and T2 (end of treatment, 1.5 years). T0-T1 hormone changes were correlated with T1-T2 anthropometric changes.Results: Initial weight loss at T1 was maintained at T2 (−5.0%, p < 0.001), and accompanied by decreased leptin and insulin levels at T1 and T2 (all p < 0.05) compared to T0. Most short-term signals were not affected. Only PP levels were decreased at T2 compared to T0 (p < 0.05). Most changes in hormone levels during initial weight loss did not predict subsequent changes in anthropometrics, except for T0-T1 decreases in FGF21 levels and T0-T1 increases in HMW adiponectin levels tended to be associated with larger T1-T2 increases in BMI (p < 0.05 and p = 0.05, respectively).Conclusion: CLI-induced weight loss was associated with changes in levels of long-term adiposity-related hormones towards healthy levels, but not with orexigenic changes in most short-term appetite signals. Our data indicates that the clinical impact of alterations in appetite-regulating hormones during modest weight loss remains questionable. Future studies should investigate potential associations of weight-loss-induced changes in FGF21 and adiponectin levels with weight regain.

Background: Bariatric or weight loss surgery is currently the most effective treatment for obesity and metabolic disease. Unlike dieting and pharmacology, its beneficial effects are sustained over decades in most patients, and mortality is among the lowest for major surgery. Because there are not nearly enough surgeons to implement bariatric surgery on a global scale, intensive research efforts have begun to identify its mechanisms of action on a molecular level in order to replace surgery with targeted behavioral or pharmacological treatments. To date, however, there is no consensus as to the critical mechanisms involved. Scope of review: The purpose of this non-systematic review is to evaluate the existing evidence for specific molecular and inter-organ signaling pathways that play major roles in bariatric surgery-induced weight loss and metabolic benefits, with a focus on Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), in both humans and rodents. Major conclusions: Gut-brain communication and its brain targets of food intake control and energy balance regulation are complex and redundant. Although the relatively young science of bariatric surgery has generated a number of hypotheses, no clear and unique mechanism has yet emerged. It seems increasingly likely that the broad physiological and behavioral effects produced by bariatric surgery do not involve a single mechanism, but rather multiple signaling pathways. Besides a need to improve and better validate surgeries in animals, advanced techniques, including inducible, tissue-specific knockout models, and the use of humanized physiological traits will be necessary. State-of-the-art genetically-guided neural identification techniques should be used to more selectively manipulate function-specific pathways.

This study investigates freeze-dried okra seed flour (OSF) as a functional ingredient to attenuate postprandial blood glucose rise by creating lower glycemic index (GI) rice noodles. Secondary objectives are postprandial gut hormone responses, noodle satiety, and sensory evaluation. Twenty healthy individuals consumed control rice noodle (CON), 10 % okra seed fortified noodle (OKN), 20 % OKN and glucose reference drinks on separate visits. 20 % OKN significantly lowered the postprandial glucose and insulin peaks compared to CON. Compared to CON, there was a 20-point reduction of GI value for 20 % OKN to 64. All noodles produced similar responses in postprandial ghrelin and glucagon-like peptide-1 (GLP-1). OKN were found to be more satiating than control noodles given the same amount of available carbohydrates. Sensory evaluation revealed that OSF can be added to noodle to create sensorially acceptable products, though ratings for sensory characteristics decreased with increased fortification.

PURPOSE OF REVIEW:Luminal chemosensing is a term used to describe how small molecules in the gut lumen interact with the host through surface receptors or via transport into the submucosa. In this review, we have summarized recent advances of understanding luminal chemosensing in the gastroduodenal mucosa, with a particular emphasis on how chemosensing affects mucosal protective responses and the metabolic syndrome. RECENT FINDINGS:In the past decade, data have supported the hypothesis that gut luminal chemosensing not only is important for the local or remote regulation of gut function but also contributes to the systemic regulation of metabolism, energy balance and food intake. We have provided examples of how luminal nutrients such as long-chain fatty acids (LCFAs), endogenous compounds such as bile acids, bacterial metabolites such as short-chain fatty acids (SCFAs) and bacterial components such as lipopolysaccharide (LPS) activate cognate receptors expressed on key effector cells such as enteroendocrine cells and inflammatory cells in order to profoundly affect organ function through the initiation or suppression of inflammatory pathways, altering gut barrier function and nutrient uptake, altering gut motility and visceral pain pathways, and preventing mucosal injury. SUMMARY:These recent discoveries in this area have provided new possibilities for identifying novel molecular targets for the treatment of mucosal injury, metabolic disorders and abnormal visceral sensation. Understanding luminal chemosensory mechanisms may help to identify novel molecular targets for the treatment and prevention of mucosal injury, metabolic disorders and abnormal visceral sensation.

Introduction: Metabolic Syndrome (MetS) represents a common dysmetabolic state in children with obesity. Although data in youth show a role of gut hormones (GH) in the risk of developing MetS, no data are available during the prepubertal age, especially across clusters of MetS. Methods: We characterized components of MetS and changes in GH concentrations in 90 prepubertal children with obesity compared to 30 healthy age- and gender-matched peers. Children with obesity were divided into three groups according to the number of the components of MetS (group 1: 30 obese without components of MetS; group 2: 30 obese with 1 component of MetS; group 3: 30 obese with 2 or more components of MetS). Anthropometric parameters, blood pressure (BP), fasting insulin and glycemia, lipid profile, transaminases, and GH concentration were determined. Differences across the groups were evaluated by the Kruskal-Wallis test and post hoc analysis by Mann-Whitney test. Results: Fasting glycemia and insulin, HOMA-IR, triglycerides, and BP progressively increased and high-density lipoprotein progressively decreased across the groups of children with obesity compared to controls, showing worse values in group 3. GLP-1 and ghrelin values progressively decreased and obestatin progressively increased. The more components of the MetS were present, the further GH concentrations deviated from standard values. Discussion and Conclusion: Components of MetS and GH concentrations are impaired in prepubertal children with obesity compared to controls. The close association between progressive alterations in GH levels and increasing number of components of the MetS might indicate a role of these hormones in the determination of metabolic risk. [ABSTRACT FROM AUTHOR]

Obesity, excess adipose tissue accumulation that may impair health, is a major global healthcare challenge that increases the risk of several life-limiting diseases, reduces quality of life and leads to premature mortality. Weight loss improves or leads to the resolution of obesity-related diseases. Lifestyle interventions are the cornerstone for all weight management programmes and lead to health benefits. However, for the majority of people with severe obesity, lifestyle interventions and currently available anti-obesity medications lead to insufficient weight loss to improve their health. For these patients the only effective treatment option is bariatric surgery, which whilst highly effective, is difficult to access and not suitable for everyone, leaving a 'treatment gap' between lifestyle interventions and bariatric surgery. Unfortunately, the history of development of drugs to treat obesity has been marred by poor efficacy and safety issues. This is now set to change as a result of scientific advancements, which have increased the understanding of the role that gut hormones play in regulating energy and glucose homoeostasis. This has led to the development of effective, safe drugs based on gut hormones that target the body's own appetite regulating systems that herald a new era of treatments for people living with obesity. [ABSTRACT FROM AUTHOR]

The gut is traditionally recognized as the central organ for the digestion and absorption of nutrients, however, it also functions as a significant endocrine organ, secreting a variety of hormones such as glucagon-like peptide 1, serotonin, somatostatin, and glucocorticoids. These gut hormones, produced by specialized intestinal epithelial cells, are crucial not only for digestive processes but also for the regulation of a wide range of physiological functions, including appetite, metabolism, and immune responses. While gut hormones can exert systemic effects, they also play a pivotal role in maintaining local homeostasis within the gut. This review discusses the role of the gut as an endocrine organ, emphasizing the stimuli, the newly discovered functions, and the clinical significance of gut-secreted hormones. Deciphering the emerging role of gut hormones will lead to a better understanding of gut homeostasis, innovative treatments for disorders in the gut, as well as systemic diseases., Competing Interests: DECLARATION OF COMPETING INTERESTS The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Scope: Inflorescences of the female hop plant (Humulus lupulus L.) contain biologically active compounds, most of which have a bitter taste. Given the rising global obesity rates, there is much increasing interest in bitter taste receptors (TAS2Rs). Intestinal TAS2Rs can have beneficial effects on obesity when activated by bitter agonists. This study aims to investigate the mechanism of action of a hydroalcoholic hop extract in promoting hormone secretion that reduces the sense of hunger at the intestinal level through the interaction with TAS2Rs., Methods and Results: The results demonstrate that the hop extract is a rich source of bitter compounds (mainly α-, β-acids) that stimulate the secretion of anorexigenic peptides (glucagon-like peptide 1 [GLP-1], cholecystokinin [CCK]) in a calcium-dependent manner while reducing levels of hunger-related hormones like ghrelin. This effect is mediated through interaction with TAS2Rs, particularly Tas2r138 and Tas2r120, and through the activation of downstream signaling cascades. Knockdown of these receptors using siRNA transfection and inhibition of Trpm5, Plcβ-2, and other calcium channels significantly reduces the hop-induced calcium response as well as GLP-1 and CCK secretion., Conclusions: This study provides a potential application of H. lupulus extract for the formulation of food supplements with satiating activity capable of preventing or combating obesity., (© 2024 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

The potential mechanisms involved in lactate's role in exercise-induced appetite suppression require further examination. We used sodium bicarbonate (NaHCO 3 ) supplementation in a double-blind, placebo-controlled, randomized crossover design to explore lactate's role on neuropeptide Y (NPY), agouti-related peptide (AgRP), and alpha-melanocyte-stimulating hormone (α-MSH) concentrations. Twelve adults (7 males; 24.2 ± 3.4 kg·m -2 ; 42.18 ± 8.56 mL·kg -1 ·min -1 ) completed two identical high-intensity interval training sessions following ingestion of NaHCO 3 (BICARB) or sodium chloride (PLACEBO) pre-exercise. Blood lactate, acylated ghrelin, NPY, AgRP, α-MSH, and appetite perceptions were measured pre-exercise, 0-, 30-, 60-, and 90-min postexercise. Free-living energy intake (electronic food diaries) was measured the day before, of, and after each experimental session. In BICARB, blood lactate was greater postexercise ( P < 0.002, d > 0.70), though acylated ghrelin was similar ( P = 0.075, [Formula: see text] = 0.206) at all time points postexercise ( P > 0.034, d < 0.22). NPY ( P = 0.006, [Formula: see text] > 0.509) and AgRP ( P < 0.001, [Formula: see text] > 0.488) had main effects of time increasing following exercise and returning to baseline, with no differences between sessions (NPY: P = 0.0.192, [Formula: see text] = 0.149; AgRP: P = 0.422, [Formula: see text] = 0.060). α-MSH had no main effect of time ( P = 0.573, [Formula: see text] = 0.063) or session ( P = 0.269, [Formula: see text] = 0.110). Appetite perceptions were similar during BICARB and PLACEBO ( P = 0.007, d = 0.28), increasing in both sessions postexercise ( P < 0.088, d > 0.57). Energy intake had a main effect of day ( P = 0.025, [Formula: see text] = 0.825), where the experimental session day was greater than the day before ( P = 0.010, d = 0.59) with no other differences between days ( P > 0.260, d < 0.38). The lower accumulation of lactate than our previous work did not generate exercise-induced appetite suppression as there were no differences in acylated ghrelin, appetite perceptions, or peripheral concentrations of neuropeptides. NEW & NOTEWORTHY Current evidence supports lactate's role in exercise-induced appetite suppression. Here, we demonstrate a smaller degree of lactate accumulation with sodium bicarbonate ingestion and HIIT than our previous work and no subsequent suppression of acylated ghrelin concentrations, subjective appetite perceptions, or peripheral concentrations of neuropeptides. These results suggest either changes in central appetite-regulating neuropeptides are not reflected peripherally or the smaller magnitude of lactate accumulation did not generate exercise-induced appetite suppression as seen previously.

Aim: To assess the impact of the sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor empagliflozin (25 mg once‐daily), dietary energy restriction, or both combined, on circulating appetite‐regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity. Materials and Methods: In a double‐blind, placebo‐controlled trial, 68 adults (aged 30‐75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0%‐10.0% [42‐86 mmol/mol]) and body mass index of 25 kg/m2 or higher were randomized to (a) placebo only, (b) placebo plus diet, (c) empagliflozin only or (d) empagliflozin plus diet for 24 weeks. Dietary energy restriction matched the estimated energy deficit elicited by SGLT2 inhibitor therapy through urinary glucose excretion (~360 kcal/day). The primary outcome was change in postprandial circulating total peptide‐YY (PYY) during a 3‐hour mixed‐meal tolerance test from baseline to 24 weeks. Postprandial total glucagon‐like peptide‐1 (GLP‐1), acylated ghrelin and subjective appetite perceptions formed secondary outcomes, along with other key components of energy balance. Results: The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22 and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only (mean difference [95% CI]: −8.6 [−28.6 to 11.4], 13.4 [−6.1 to 33.0] and 1.0 [−18.0 to 19.9] pg/ml in placebo‐plus diet, empagliflozin‐only and empagliflozin‐plus‐diet groups, respectively [all P ≥.18]). Similarly, there was no consistent pattern of difference between groups for postprandial total GLP‐1, acylated ghrelin and subjective appetite perceptions. Conclusions: In people with T2D and overweight or obesity, changes in postprandial appetite‐regulatory gut peptides may not underpin the less than predicted weight loss observed with empagliflozin therapy. Clinical Trials Registration: NCT02798744, www.ClinicalTrials.gov; 2015‐001594‐40, www.EudraCT.ema.europa.eu; ISRCTN82062639, www.ISRCTN.org. [ABSTRACT FROM AUTHOR]

Despite decades of obesity research and various public health initiatives, obesity remains a major public health concern. Our most drastic but most effective treatment of obesity is bariatric surgery with weight loss and improvements in co-morbidities, including resolution of type 2 diabetes (T2D). However, the mechanisms by which surgery elicits metabolic benefits are still not well understood. One proposed mechanism is through signals generated by the intestine (nutrients, neuronal, and/or endocrine) that communicate nutrient status to the brain. In this review, we discuss the contributions of gut-brain communication to the physiological regulation of body weight and its impact on the success of bariatric surgery. Advancing our understanding of the mechanisms that drive bariatric surgery-induced metabolic benefits will ultimately lead to the identification of novel, less invasive strategies to treat obesity. [ABSTRACT FROM AUTHOR]

Background: Plausible phenotype mechanisms following bariatric surgery include changes in neural and gastrointestinal physiology. This pilot study aims to investigate individual and combined neurologic, gut microbiome, and plasma hormone changes pre- versus post-vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), and medical weight loss (MWL). We hypothesized post-weight loss phenotype would be associated with changes in central reward system brain connectivity, differences in postprandial gut hormone responses, and increased gut microbiome diversity. Methods: Subjects included participants undergoing VSG, n = 7; RYGB, n = 9; and MWL, n = 6. Ghrelin, glucagon-like peptide-1, peptide-YY, gut microbiome, and resting state functional magnetic resonance imaging (rsfMRI; using fractional amplitude of low-frequency fluctuations [fALFF]) were measured pre- and post-intervention in fasting and fed states. We explored phenotype characterization using clustering on gut hormone, microbiome, and rsfMRI datasets and a combined analysis. Results: We observed more widespread fALFF differences post-bariatric surgery versus post-MWL. Decreased post-prandial fALFF was seen in food reward regions post-RYGB. The highest number of microbial taxa that increased post-intervention occurred in the RYGB group, followed by VSG and MWL. The combined hormone, microbiome, and MRI dataset most accurately clustered samples into pre- versus post-VSG phenotypes followed by RYGB subjects. Conclusion: The data suggest surgical weight loss (VSG and RYGB) has a bigger impact on brain and gut function versus MWL and leads to lesser post-prandial activation of food-related neural circuits. VSG subjects had the greatest phenotype differences in interactions of microbiome, rsfMRI, and gut hormone features, followed by RYGB and MWL. These results will inform future prospective research studying gut-brain changes post-bariatric surgery. [ABSTRACT FROM AUTHOR]

The age-related decline in appetite and food intake – termed "anorexia of ageing" – is implicated in undernutrition in later life and hence provides a public health challenge for our ageing population. Eating behaviour is controlled, in part, by homeostatic mechanisms which sense nutrient status and provide feedback to appetite control regions of the brain. Such feedback signals, propagated by episodic gut hormones, are dysregulated in some older adults. The secretory responses of appetite-related gut hormones to feeding are amplified, inducing a more anorexigenic signal which is associated with reduced appetite and food intake. Such an augmented response would indicate an increase in gut sensitivity to nutrients. Consequently, this review explores the role of gastrointestinal tract nutrient sensing in age-related appetite dysregulation. We review and synthesise evidence for age-related alterations in nutrient sensing which may explain the observed hormonal dysregulation. Drawing on what is known regarding elements of nutrient sensing pathways in animal models, in other tissues of the body, and in certain models of disease, we identify potential causal mechanisms including alterations in enteroendocrine cell number and distribution, dysregulation of cell signalling pathways, and changes in the gut milieu. From identified gaps in evidence, we highlight interesting and important avenues for future research. • Anorexia of ageing is the loss of appetite and reduction in food intake experienced by approximately one in three older adults. • The mechanisms underpinning age-related reductions in appetite and food intake remain poorly understood. • Appetite-suppressed older adults, but not those with a healthy appetite, exhibit augmented gut hormone responses to food. • This is indicative of gut hypersensitivity in nutrient sensing, and dysregulation of nutrient sensing processes. • Possible mechanisms of dysregulation include alterations in: EEC number, cell signalling, and gut luminal environment. [ABSTRACT FROM AUTHOR]

Because of differential processing of the hormone precursor, proglucagon, numerous peptide products are released from the pancreatic alpha cells and the intestinal L-cells in which the (pro)glucagon gene is expressed. Of particular interest in relation to obesity are glucagon from the pancreas and oxyntomodulin and GLP-1 from the gut, all of which inhibit food intake, but the other products are also briefly discussed, because knowledge about these is required for selection and evaluation of the methods for measurement of the hormones. The distal intestinal L-cells also secrete the appetite-inhibiting hormone PYY. Characteristics of the secretion of the pancreatic and intestinal products are described, and causes of the hypersecretion of glucagon in obesity and type 2 diabetes are discussed. In contrast, the secretion of the products of the L-cells is generally impaired in obesity, raising questions about their role in the development of obesity. It is concluded that the impairment probably is secondary to obesity, but the lower plasma levels may contribute to the development.

Purpose: Decreased circulating levels of food-intake-regulating gut hormones have been observed in type 2 diabetes and obesity. However, it is still unknown if this is due to decreased secretion from the gut mucosal cells or due to extra-intestinal processing of hormones. Methods: We measured intestinal hormone content and assessed morphological differences in the intestinal mucosa by histology and immunohistochemistry. Secretion of hormones and absorption of glucose and bile acids (BA) were assessed in isolated perfused mouse intestine. Results: GIP (glucose-dependent insulinotropic polypeptide) and SS (somatostatin) contents were higher in the duodenum of control mice (p < 0.001, and <0.01). Duodenal GLP-1 (glucagon-like peptide-1) content (p < 0.01) and distal ileum PYY content were higher in DIO mice (p < 0.05). Villus height in the jejunum, crypt depth, and villus height in the ileum were increased in DIO mice (p < 0.05 and p = 0.001). In the distal ileum of DIO mice, more immunoreactive GLP-1 and PYY cells were observed (p = 0.01 and 0.007). There was no difference in the absorption of glucose and bile acids. Distal secretion of SS tended to be higher in DIO mice (p < 0.058), whereas no difference was observed for the other hormones in response to glucose or bile acids. Conclusion: Our data suggest that differences regarding production and secretion are unlikely to be responsible for the altered circulating gut hormone levels in obesity, since enteroendocrine morphology and hormone secretion capacity were largely unaffected in DIO mice. [ABSTRACT FROM AUTHOR]