Special Issue "Appetite and Satiety Control-Gut Mechanisms"

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (15 January 2021).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Christine Feinle-Bisset
E-Mail Website
Guest Editor
Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide, Australia
Interests: appetite regulation in humans; gastrointestinal function; gut hormones; gastric emptying; GI motility; dietary nutrients; obesity
Prof. Dr. Michael Horowitz
E-Mail Website
Guest Editor
Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical School, The University of Adelaide, and Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
Interests: endocrinology; diabetes; gastrointestinal motility; gastroparesis; glycaemic control; obesity; nutrition

Special Issue Information

Dear Colleagues,

With the continued rise in the prevalence of obesity and its comorbidities, type 2 diabetes, and cardiovascular and hepatic disease, and the recognition that therapeutic options for both prevention and management are suboptimal, an improved understanding of the mechanisms that regulate appetite and energy intake is of pivotal importance.

Appetite and energy intake are modulated by a diverse range of factors. These include physiological mechanisms, such as acute changes in the release of gut hormones, slowing of gastric emptying, and elevations in circulating levels of metabolites, the physicochemical properties of food, and environmental influences.

This Special Issue will collate recent high-quality research in the field of appetite regulation, focussing on the investigation of gut-related mechanisms, including nutrient sensing, gut hormones, gastrointestinal motility, gut–brain communication, and roles of the vagus, diet, and the microbiome. Both original research articles and reviews spanning clinical and preclinical work are welcome.


Prof. Dr. Christine Feinle-Bisset
Prof. Michael Horowitz
Guest Editors

Manuscript Submission Information

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Keywords

  • eating behaviour
  • appetite
  • food intake
  • energy intake
  • satiation/satiety
  • gut mechanisms
  • appetite-regulatory hormones
  • gut hormones
  • gut functions
  • gastric emptying
  • intestinal nutrient sensing
  • dietary changes
  • gut–brain communication
  • gut microbiome
  • human
  • animal/preclinical
  • obesity
  • type 2 diabetes.

Published Papers (26 papers)

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Editorial

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Editorial
Appetite and Satiety Control—Contribution of Gut Mechanisms
Nutrients 2021, 13(10), 3635; https://doi.org/10.3390/nu13103635 - 17 Oct 2021
Viewed by 608
Abstract
The prevalence of obesity, and its comorbidities, particularly type 2 diabetes, cardiovascular and hepatic disease and certain cancers, continues to rise at an alarming rate worldwide [...] Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)

Research

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Article
Effect of Obesity on the Expression of Nutrient Receptors and Satiety Hormones in the Human Colon
Nutrients 2021, 13(4), 1271; https://doi.org/10.3390/nu13041271 - 13 Apr 2021
Cited by 2 | Viewed by 946
Abstract
Background: Receptors located on enteroendocrine cells (EECs) of the colon can detect nutrients in the lumen. These receptors regulate appetite through a variety of mechanisms, including hormonal and neuronal signals. We assessed the effect of obesity on the expression of these G-protein coupled [...] Read more.
Background: Receptors located on enteroendocrine cells (EECs) of the colon can detect nutrients in the lumen. These receptors regulate appetite through a variety of mechanisms, including hormonal and neuronal signals. We assessed the effect of obesity on the expression of these G-protein coupled receptors (GPCRs) and hormones at both mRNA and protein level. Methods: qPCR and immunohistochemistry were used to examine colonic tissue from cohorts of patients from the Netherlands (proximal and sigmoid tissue) and the United Kingdom (tissue from across the colon) and patients were grouped by body mass index (BMI) value (BMI < 25 and BMI ≥ 25). Results: The mRNA expression of the hormones/signaling molecules serotonin, glucagon, peptide YY (PYY), CCK and somatostatin were not significantly different between BMI groups. GPR40 mRNA expression was significantly increased in sigmoid colon samples in the BMI ≥ 25 group, but not proximal colon. GPR41, GPR109a, GPR43, GPR120, GPRC6A, and CaSR mRNA expression were unaltered between low and high BMI. At the protein level, serotonin and PYY containing cell numbers were similar in high and low BMI groups. Enterochromaffin cells (EC) showed high degree of co-expression with amino acid sensing receptor, CaSR while co-expression with PYY containing L-cells was limited, regardless of BMI. Conclusions: While expression of medium/long chain fatty acid receptor GPR40 was increased in the sigmoid colon of the high BMI group, expression of other nutrient sensing GPCRs, and expression profiles of EECs involved in peripheral mechanisms of appetite regulation were unchanged. Collectively, these data suggest that in human colonic tissue, EEC and nutrient-sensing receptor expression profiles are not affected despite changes to BMI. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Article
Abdominothoracic Postural Tone Influences the Sensations Induced by Meal Ingestion
Nutrients 2021, 13(2), 658; https://doi.org/10.3390/nu13020658 - 18 Feb 2021
Cited by 3 | Viewed by 950
Abstract
Postprandial objective abdominal distention is frequently associated with a subjective sensation of abdominal bloating, but the relation between both complaints is unknown. While the bloating sensation has a visceral origin, abdominal distention is a behavioral somatic response, involving contraction and descent of the [...] Read more.
Postprandial objective abdominal distention is frequently associated with a subjective sensation of abdominal bloating, but the relation between both complaints is unknown. While the bloating sensation has a visceral origin, abdominal distention is a behavioral somatic response, involving contraction and descent of the diaphragm with protrusion of the anterior abdominal wall. Our aim was to determine whether abdominal distention influences digestive sensations. In 16 healthy women we investigated the effect of intentional abdominal distention on experimentally induced bloating sensation (by a meal overload). Participants were first taught to produce diaphragmatic contraction and visible abdominal distention. After a meal overload, sensations of bloating (0 to 10) and digestive well-being (−5 to + 5) were measured during 30-s. maneuvers alternating diaphragmatic contraction and diaphragmatic relaxation. Compared to diaphragmatic relaxation, diaphragmatic contraction was associated with diaphragmatic descent (by 21 + 3 mm; p < 0.001), objective abdominal distension (32 + 5 mm girth increase; p = 0.001), more intense sensation of bloating (7.3 + 0.4 vs. 8.0 + 0.4 score; p = 0.010) and lower digestive well-being (−0.9 + 0.5 vs. −1.9 + 0.5 score; p = 0.028). These results indicate that somatic postural tone underlying abdominal distention worsens the perception of visceral sensations (ClinicalTrials.gov ID: NCT04691882). Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Article
Modulation of Food Intake by Differential TAS2R Stimulation in Rat
Nutrients 2020, 12(12), 3784; https://doi.org/10.3390/nu12123784 - 10 Dec 2020
Cited by 5 | Viewed by 1054
Abstract
Metabolic surgery modulates the enterohormone profile, which leads, among other effects, to changes in food intake. Bitter taste receptors (TAS2Rs) have been identified in the gastrointestinal tract and specific stimulation of these has been linked to the control of ghrelin secretion. We hypothesize [...] Read more.
Metabolic surgery modulates the enterohormone profile, which leads, among other effects, to changes in food intake. Bitter taste receptors (TAS2Rs) have been identified in the gastrointestinal tract and specific stimulation of these has been linked to the control of ghrelin secretion. We hypothesize that optimal stimulation of TAS2Rs could help to modulate enteroendocrine secretions and thus regulate food intake. To determine this, we have assayed the response to specific agonists for hTAS2R5, hTAS2R14 and hTAS2R39 on enteroendocrine secretions from intestinal segments and food intake in rats. We found that hTAS2R5 agonists stimulate glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK), and reduce food intake. hTAS2R14 agonists induce GLP1, while hTASR39 agonists tend to increase peptide YY (PYY) but fail to reduce food intake. The effect of simultaneously activating several receptors is heterogeneous depending on the relative affinity of the agonists for each receptor. Although detailed mechanisms are not clear, bitter compounds can stimulate differentially enteroendocrine secretions that modulate food intake in rats. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Article
Appetite Control across the Lifecourse: The Acute Impact of Breakfast Drink Quantity and Protein Content. The Full4Health Project
Nutrients 2020, 12(12), 3710; https://doi.org/10.3390/nu12123710 - 30 Nov 2020
Cited by 3 | Viewed by 2469
Abstract
Understanding the mechanisms of hunger, satiety and how nutrients affect appetite control is important for successful weight management across the lifecourse. The primary aim of this study was to describe acute appetite control across the lifecourse, comparing age groups (children, adolescents, adults, elderly), [...] Read more.
Understanding the mechanisms of hunger, satiety and how nutrients affect appetite control is important for successful weight management across the lifecourse. The primary aim of this study was to describe acute appetite control across the lifecourse, comparing age groups (children, adolescents, adults, elderly), weight categories, genders and European sites (Scotland and Greece). Participants (n = 391) consumed four test drinks, varying in composition (15% (normal protein, NP) and 30% (high protein, HP) of energy from protein) and quantity (based on 100% basal metabolic rate (BMR) and 140% BMR), on four separate days in a double-blind randomized controlled study. Ad libitum energy intake (EI), subjective appetite and biomarkers of appetite and metabolism (adults and elderly only) were measured. The adults’ appetite was significantly greater than that of the elderly across all drink types (p < 0.004) and in response to drink quantities (p < 0.001). There were no significant differences in EI between age groups, weight categories, genders or sites. Concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were significantly greater in the elderly than the adults (p < 0.001). Ghrelin and fasting leptin concentrations differed significantly between weight categories, genders and sites (p < 0.05), while GLP-1 and PYY concentrations differed significantly between genders only (p < 0.05). Compared to NP drinks, HP drinks significantly increased postprandial GLP-1 and PYY (p < 0.001). Advanced age was concomitant with reduced appetite and elevated anorectic hormone release, which may contribute to the development of malnutrition. In addition, appetite hormone concentrations differed between weight categories, genders and geographical locations. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Article
Whey Protein Drink Ingestion before Breakfast Suppressed Energy Intake at Breakfast and Lunch, but Not during Dinner, and Was Less Suppressed in Healthy Older than Younger Men
Nutrients 2020, 12(11), 3318; https://doi.org/10.3390/nu12113318 - 29 Oct 2020
Cited by 2 | Viewed by 1460
Abstract
Ageing is associated with changes in feeding behavior. We have reported that there is suppression of energy intake three hours after whey protein drink ingestion in young, but not older, men. This study aimed to determine these effects over a time period of [...] Read more.
Ageing is associated with changes in feeding behavior. We have reported that there is suppression of energy intake three hours after whey protein drink ingestion in young, but not older, men. This study aimed to determine these effects over a time period of 9 h. Fifteen younger (27 ± 1 years, 25.8 ± 0.7 kg/m2) and 15 older (75 ± 2 years, 26.6 ± 0.8 kg/m2) healthy men were studied on three occasions on which they received, in a randomized order, a 30 g/120 kcal, 70 g/280 kcal whey-protein, or control (~2 kcal) drink. Ad-libitum energy intake (sum of breakfast, lunch, and dinner) was suppressed in a protein load responsive fashion (P = 0.001). Suppression was minimal at breakfast, substantial at lunch (~−16%, P = 0.001), no longer present by dinner, and was less in older than younger men (−3 ± 4% vs. −8 ± 4%, P = 0.027). Cumulative protein intake was increased in the younger and older men (+20% and +42%, P < 0.001). Visual analogue scale ratings of fullness were higher and desire to eat and prospective food consumption were lower after protein vs. control, and these effects were smaller in older vs. younger men (interaction effect P < 0.05). These findings support the use of whey-protein drink supplements in older people who aim to increase their protein intake without decreasing their overall energy intake. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Article
Cannabinoid CB1 Receptors in the Intestinal Epithelium Are Required for Acute Western-Diet Preferences in Mice
Nutrients 2020, 12(9), 2874; https://doi.org/10.3390/nu12092874 - 20 Sep 2020
Cited by 7 | Viewed by 1599
Abstract
The endocannabinoid system plays an important role in the intake of palatable food. For example, endocannabinoid signaling in the upper small-intestinal epithelium is increased (i) in rats after tasting dietary fats, which promotes intake of fats, and (ii) in a mouse model of [...] Read more.
The endocannabinoid system plays an important role in the intake of palatable food. For example, endocannabinoid signaling in the upper small-intestinal epithelium is increased (i) in rats after tasting dietary fats, which promotes intake of fats, and (ii) in a mouse model of diet-induced obesity, which promotes overeating via impaired nutrient-induced gut–brain satiation signaling. We now utilized a combination of genetic, pharmacological, and behavioral approaches to identify roles for cannabinoid CB1Rs in upper small-intestinal epithelium in preferences for a western-style diet (WD, high-fat/sucrose) versus a standard rodent diet (SD, low-fat/no sucrose). Mice were maintained on SD in automated feeding chambers. During testing, mice were given simultaneous access to SD and WD, and intakes were recorded. Mice displayed large preferences for the WD, which were inhibited by systemic pretreatment with the cannabinoid CB1R antagonist/inverse agonist, AM251, for up to 3 h. We next used our novel intestinal epithelium-specific conditional cannabinoid CB1R-deficient mice (IntCB1−/−) to investigate if intestinal CB1Rs are necessary for WD preferences. Similar to AM251 treatment, preferences for WD were largely absent in IntCB1−/− mice when compared to control mice for up to 6 h. Together, these data suggest that CB1Rs in the murine intestinal epithelium are required for acute WD preferences. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Article
The Effect of Isoleucine Supplementation on Body Weight Gain and Blood Glucose Response in Lean and Obese Mice
Nutrients 2020, 12(8), 2446; https://doi.org/10.3390/nu12082446 - 14 Aug 2020
Cited by 6 | Viewed by 1499
Abstract
Chronic isoleucine supplementation prevents diet-induced weight gain in rodents. Acute-isoleucine administration improves glucose tolerance in rodents and reduces postprandial glucose levels in humans. However, the effect of chronic-isoleucine supplementation on body weight and glucose tolerance in obesity is unknown. This study aimed to [...] Read more.
Chronic isoleucine supplementation prevents diet-induced weight gain in rodents. Acute-isoleucine administration improves glucose tolerance in rodents and reduces postprandial glucose levels in humans. However, the effect of chronic-isoleucine supplementation on body weight and glucose tolerance in obesity is unknown. This study aimed to investigate the impact of chronic isoleucine on body weight gain and glucose tolerance in lean and high-fat-diet (HFD) induced-obese mice. Male C57BL/6-mice, fed a standard-laboratory-diet (SLD) or HFD for 12 weeks, were randomly allocated to: (1) Control: Drinking water; (2) Acute: Drinking water with a gavage of isoleucine (300 mg/kg) prior to the oral-glucose-tolerance-test (OGTT) or gastric-emptying-breath-test (GEBT); (3) Chronic: Drinking water with 1.5% isoleucine, for a further six weeks. At 16 weeks, an OGTT and GEBT was performed and at 17 weeks metabolic monitoring. In SLD- and HFD-mice, there was no difference in body weight, fat mass, and plasma lipid profiles between isoleucine treatment groups. Acute-isoleucine did not improve glucose tolerance in SLD- or HFD-mice. Chronic-isoleucine impaired glucose tolerance in SLD-mice. There was no difference in gastric emptying between any groups. Chronic-isoleucine did not alter energy intake, energy expenditure, or respiratory quotient in SLD- or HFD-mice. In conclusion, chronic isoleucine supplementation may not be an effective treatment for obesity or glucose intolerance. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Article
Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution
Nutrients 2020, 12(7), 1962; https://doi.org/10.3390/nu12071962 - 01 Jul 2020
Cited by 5 | Viewed by 1048
Abstract
Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects [...] Read more.
Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixisenatide (10 mcg) or placebo subcutaneously, in a randomised, double-blind, crossover design. GE and intragastric distribution were measured for 180 min followed by a buffet-style meal, where EI was quantified. Relationships of EI with total, proximal, and distal stomach content were assessed. In both groups, lixisenatide slowed GE markedly, with increased retention in both the proximal (p < 0.001) and distal (p < 0.001) stomach and decreased EI (p < 0.001). EI was not related to the content of the total or proximal stomach but inversely related to the distal stomach at 180 min in health on placebo (r = −0.58, p = 0.03) but not in T2D nor after lixisenatide in either group. In healthy and T2D participants, the reduction in EI by lixisenatide is unrelated to changes in GE/intragastric distribution, consistent with a centrally mediated effect. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review

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Review
Microbiota’s Role in Diet-Driven Alterations in Food Intake: Satiety, Energy Balance, and Reward
Nutrients 2021, 13(9), 3067; https://doi.org/10.3390/nu13093067 - 31 Aug 2021
Cited by 2 | Viewed by 1578
Abstract
The gut microbiota plays a key role in modulating host physiology and behavior, particularly feeding behavior and energy homeostasis. There is accumulating evidence demonstrating a role for gut microbiota in the etiology of obesity. In human and rodent studies, obesity and high-energy feeding [...] Read more.
The gut microbiota plays a key role in modulating host physiology and behavior, particularly feeding behavior and energy homeostasis. There is accumulating evidence demonstrating a role for gut microbiota in the etiology of obesity. In human and rodent studies, obesity and high-energy feeding are most consistently found to be associated with decreased bacterial diversity, changes in main phyla relative abundances and increased presence of pro-inflammatory products. Diet-associated alterations in microbiome composition are linked with weight gain, adiposity, and changes in ingestive behavior. There are multiple pathways through which the microbiome influences food intake. This review discusses these pathways, including peripheral mechanisms such as the regulation of gut satiety peptide release and alterations in leptin and cholecystokinin signaling along the vagus nerve, as well as central mechanisms, such as the modulation of hypothalamic neuroinflammation and alterations in reward signaling. Most research currently focuses on determining the role of the microbiome in the development of obesity and using microbiome manipulation to prevent diet-induced increase in food intake. More studies are necessary to determine whether microbiome manipulation after prolonged energy-dense diet exposure and obesity can reduce intake and promote meaningful weight loss. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
The Function of Gastrointestinal Hormones in Obesity—Implications for the Regulation of Energy Intake
Nutrients 2021, 13(6), 1839; https://doi.org/10.3390/nu13061839 - 27 May 2021
Cited by 3 | Viewed by 1764
Abstract
The global burden of obesity and the challenges of prevention prompted researchers to investigate the mechanisms that control food intake. Food ingestion triggers several physiological responses in the digestive system, including the release of gastrointestinal hormones from enteroendocrine cells that are involved in [...] Read more.
The global burden of obesity and the challenges of prevention prompted researchers to investigate the mechanisms that control food intake. Food ingestion triggers several physiological responses in the digestive system, including the release of gastrointestinal hormones from enteroendocrine cells that are involved in appetite signalling. Disturbed regulation of gut hormone release may affect energy homeostasis and contribute to obesity. In this review, we summarize the changes that occur in the gut hormone balance during the pre- and postprandial state in obesity and the alterations in the diurnal dynamics of their plasma levels. We further discuss how obesity may affect nutrient sensors on enteroendocrine cells that sense the luminal content and provoke alterations in their secretory profile. Gastric bypass surgery elicits one of the most favorable metabolic outcomes in obese patients. We summarize the effect of different strategies to induce weight loss on gut enteroendocrine function. Although the mechanisms underlying obesity are not fully understood, restoring the gut hormone balance in obesity by targeting nutrient sensors or by combination therapy with gut peptide mimetics represents a novel strategy to ameliorate obesity. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Review on the Regional Effects of Gastrointestinal Luminal Stimulation on Appetite and Energy Intake: (Pre)clinical Observations
Nutrients 2021, 13(5), 1601; https://doi.org/10.3390/nu13051601 - 11 May 2021
Cited by 1 | Viewed by 610
Abstract
Macronutrients in the gastrointestinal (GI) lumen are able to activate “intestinal brakes”, feedback mechanisms on proximal GI motility and secretion including appetite and energy intake. In this review, we provide a detailed overview of the current evidence with respect to four questions: (1) [...] Read more.
Macronutrients in the gastrointestinal (GI) lumen are able to activate “intestinal brakes”, feedback mechanisms on proximal GI motility and secretion including appetite and energy intake. In this review, we provide a detailed overview of the current evidence with respect to four questions: (1) are regional differences (duodenum, jejunum, ileum) present in the intestinal luminal nutrient modulation of appetite and energy intake? (2) is this “intestinal brake” effect macronutrient specific? (3) is this “intestinal brake” effect maintained during repetitive activation? (4) can the “intestinal brake” effect be activated via non-caloric tastants? Recent evidence indicates that: (1) regional differences exist in the intestinal modulation of appetite and energy intake with a proximal to distal gradient for inhibition of energy intake: ileum and jejunum > duodenum at low but not at high caloric infusion rates. (2) the “intestinal brake” effect on appetite and energy appears not to be macronutrient specific. At equi-caloric amounts, the inhibition on energy intake and appetite is in the same range for fat, protein and carbohydrate. (3) data on repetitive ileal brake activation are scarce because of the need for prolonged intestinal intubation. During repetitive activation of the ileal brake for up to 4 days, no adaptation was observed but overall the inhibitory effect on energy intake was small. (4) the concept of influencing energy intake by intra-intestinal delivery of non-caloric tastants is intriguing. Among tastants, the bitter compounds appear to be more effective in influencing energy intake. Energy intake decreases modestly after post-oral delivery of bitter tastants or a combination of tastants (bitter, sweet and umami). Intestinal brake activation provides an interesting concept for preventive and therapeutic approaches in weight management strategies. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Effects of Oro-Sensory Exposure on Satiation and Underlying Neurophysiological Mechanisms—What Do We Know So Far?
Nutrients 2021, 13(5), 1391; https://doi.org/10.3390/nu13051391 - 21 Apr 2021
Cited by 1 | Viewed by 858
Abstract
The mouth is the first part of the gastrointestinal tract. During mastication sensory signals from the mouth, so-called oro-sensory exposure, elicit physiological signals that affect satiation and food intake. It has been established that a longer duration of oro-sensory exposure leads to earlier [...] Read more.
The mouth is the first part of the gastrointestinal tract. During mastication sensory signals from the mouth, so-called oro-sensory exposure, elicit physiological signals that affect satiation and food intake. It has been established that a longer duration of oro-sensory exposure leads to earlier satiation. In addition, foods with more intense sweet or salty taste induce earlier satiation compared to foods that are equally palatable, but with lower taste intensity. Oro-sensory exposure to food affects satiation by direct signaling via the brainstem to higher cortical regions involved in taste and reward, including the nucleus accumbens and the insula. There is little evidence that oro-sensory exposure affects satiation indirectly through either hormone responses or gastric signals. Critical brain areas for satiation, such as the brainstem, should be studied more intensively to better understand the neurophysiological mechanisms underlying the process of satiation. Furthermore, it is essential to increase the understanding of how of highly automated eating behaviors, such as oral processing and eating rate, are formed during early childhood. A better understanding of the aforementioned mechanisms provides fundamental insight in relation to strategies to prevent overconsumption and the development of obesity in future generations. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Effects of Bitter Substances on GI Function, Energy Intake and Glycaemia-Do Preclinical Findings Translate to Outcomes in Humans?
Nutrients 2021, 13(4), 1317; https://doi.org/10.3390/nu13041317 - 16 Apr 2021
Cited by 1 | Viewed by 886
Abstract
Bitter substances are contained in many plants, are often toxic and can be present in spoiled food. Thus, the capacity to detect bitter taste has classically been viewed to have evolved primarily to signal the presence of toxins and thereby avoid their consumption. [...] Read more.
Bitter substances are contained in many plants, are often toxic and can be present in spoiled food. Thus, the capacity to detect bitter taste has classically been viewed to have evolved primarily to signal the presence of toxins and thereby avoid their consumption. The recognition, based on preclinical studies (i.e., studies in cell cultures or experimental animals), that bitter substances may have potent effects to stimulate the secretion of gastrointestinal (GI) hormones and modulate gut motility, via activation of bitter taste receptors located in the GI tract, reduce food intake and lower postprandial blood glucose, has sparked considerable interest in their potential use in the management or prevention of obesity and/or type 2 diabetes. However, it remains to be established whether findings from preclinical studies can be translated to health outcomes, including weight loss and improved long-term glycaemic control. This review examines information relating to the effects of bitter substances on the secretion of key gut hormones, gastric motility, food intake and blood glucose in preclinical studies, as well as the evidence from clinical studies, as to whether findings from animal studies translate to humans. Finally, the evidence that bitter substances have the capacity to reduce body weight and/or improve glycaemic control in obesity and/or type 2 diabetes, and potentially represent a novel strategy for the management, or prevention, of obesity and type 2 diabetes, is explored. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Rational Use of Protein Supplements in the Elderly—Relevance of Gastrointestinal Mechanisms
Nutrients 2021, 13(4), 1227; https://doi.org/10.3390/nu13041227 - 08 Apr 2021
Cited by 2 | Viewed by 1104
Abstract
Protein supplements are increasingly used by older people to maintain nutrition and prevent or treat loss of muscle function. Daily protein requirements in older people are in the range of 1.2 gm/kg/day or higher. Many older adults do not consume this much protein [...] Read more.
Protein supplements are increasingly used by older people to maintain nutrition and prevent or treat loss of muscle function. Daily protein requirements in older people are in the range of 1.2 gm/kg/day or higher. Many older adults do not consume this much protein and are likely to benefit from higher consumption. Protein supplements are probably best taken twice daily, if possible soon after exercise, in doses that achieve protein intakes of 30 gm or more per episode. It is probably not important to give these supplements between meals, as we have shown no suppressive effects of 30 gm whey drinks, and little if any suppression of 70 gm given to older subjects at varying time intervals from meals. Many gastrointestinal mechanisms controlling food intake change with age, but their contributions to changes in responses to protein are not yet well understood. There may be benefits in giving the supplement with rather than between meals, to achieve protein intakes above the effective anabolic threshold with lower supplement doses, and have favourable effects on food-induced blood glucose increases in older people with, or at risk of developing, type 2 diabetes mellitus; combined protein and glucose drinks lower blood glucose compared with glucose alone in older people. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
Review
Endocannabinoids and the Gut-Brain Control of Food Intake and Obesity
Nutrients 2021, 13(4), 1214; https://doi.org/10.3390/nu13041214 - 07 Apr 2021
Cited by 10 | Viewed by 1215
Abstract
Gut-brain signaling controls food intake and energy homeostasis, and its activity is thought to be dysregulated in obesity. We will explore new studies that suggest the endocannabinoid (eCB) system in the upper gastrointestinal tract plays an important role in controlling gut-brain neurotransmission carried [...] Read more.
Gut-brain signaling controls food intake and energy homeostasis, and its activity is thought to be dysregulated in obesity. We will explore new studies that suggest the endocannabinoid (eCB) system in the upper gastrointestinal tract plays an important role in controlling gut-brain neurotransmission carried by the vagus nerve and the intake of palatable food and other reinforcers. A focus will be on studies that reveal both indirect and direct interactions between eCB signaling and vagal afferent neurons. These investigations identify (i) an indirect mechanism that controls nutrient-induced release of peptides from the gut epithelium that directly interact with corresponding receptors on vagal afferent neurons, and (ii) a direct mechanism via interactions between eCBs and cannabinoid receptors expressed on vagal afferent neurons. Moreover, the impact of diet-induced obesity on these pathways will be considered. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Gastric Sensory and Motor Functions and Energy Intake in Health and Obesity—Therapeutic Implications
Nutrients 2021, 13(4), 1158; https://doi.org/10.3390/nu13041158 - 01 Apr 2021
Cited by 3 | Viewed by 1001
Abstract
Sensory and motor functions of the stomach, including gastric emptying and accommodation, have significant effects on energy consumption and appetite. Obesity is characterized by energy imbalance; altered gastric functions, such as rapid gastric emptying and large fasting gastric volume in obesity, may result [...] Read more.
Sensory and motor functions of the stomach, including gastric emptying and accommodation, have significant effects on energy consumption and appetite. Obesity is characterized by energy imbalance; altered gastric functions, such as rapid gastric emptying and large fasting gastric volume in obesity, may result in increased food intake prior to reaching usual fullness and increased appetite. Thus, many different interventions for obesity, including different diets, anti-obesity medications, bariatric endoscopy, and surgery, alter gastric functions and gastrointestinal motility. In this review, we focus on the role of the gastric and intestinal functions in food intake, pathophysiology of obesity, and obesity management. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease
Nutrients 2021, 13(4), 1104; https://doi.org/10.3390/nu13041104 - 28 Mar 2021
Cited by 7 | Viewed by 1807
Abstract
Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the [...] Read more.
Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward
Nutrients 2021, 13(3), 977; https://doi.org/10.3390/nu13030977 - 17 Mar 2021
Cited by 3 | Viewed by 1568
Abstract
Eating behaviors are influenced by the reinforcing properties of foods that can favor decisions driven by reward incentives over metabolic needs. These food reward-motivated behaviors are modulated by gut-derived peptides such as ghrelin and glucagon-like peptide-1 (GLP-1) that are well-established to promote or [...] Read more.
Eating behaviors are influenced by the reinforcing properties of foods that can favor decisions driven by reward incentives over metabolic needs. These food reward-motivated behaviors are modulated by gut-derived peptides such as ghrelin and glucagon-like peptide-1 (GLP-1) that are well-established to promote or reduce energy intake, respectively. In this review we highlight the antagonizing actions of ghrelin and GLP-1 on various behavioral constructs related to food reward/reinforcement, including reactivity to food cues, conditioned meal anticipation, effort-based food-motivated behaviors, and flavor-nutrient preference and aversion learning. We integrate physiological and behavioral neuroscience studies conducted in both rodents and human to illustrate translational findings of interest for the treatment of obesity or metabolic impairments. Collectively, the literature discussed herein highlights a model where ghrelin and GLP-1 regulate food reward-motivated behaviors via both competing and independent neurobiological and behavioral mechanisms. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Central Neurocircuits Regulating Food Intake in Response to Gut Inputs—Preclinical Evidence
Nutrients 2021, 13(3), 908; https://doi.org/10.3390/nu13030908 - 11 Mar 2021
Cited by 3 | Viewed by 1384
Abstract
The regulation of energy balance requires the complex integration of homeostatic and hedonic pathways, but sensory inputs from the gastrointestinal (GI) tract are increasingly recognized as playing critical roles. The stomach and small intestine relay sensory information to the central nervous system (CNS) [...] Read more.
The regulation of energy balance requires the complex integration of homeostatic and hedonic pathways, but sensory inputs from the gastrointestinal (GI) tract are increasingly recognized as playing critical roles. The stomach and small intestine relay sensory information to the central nervous system (CNS) via the sensory afferent vagus nerve. This vast volume of complex sensory information is received by neurons of the nucleus of the tractus solitarius (NTS) and is integrated with responses to circulating factors as well as descending inputs from the brainstem, midbrain, and forebrain nuclei involved in autonomic regulation. The integrated signal is relayed to the adjacent dorsal motor nucleus of the vagus (DMV), which supplies the motor output response via the efferent vagus nerve to regulate and modulate gastric motility, tone, secretion, and emptying, as well as intestinal motility and transit; the precise coordination of these responses is essential for the control of meal size, meal termination, and nutrient absorption. The interconnectivity of the NTS implies that many other CNS areas are capable of modulating vagal efferent output, emphasized by the many CNS disorders associated with dysregulated GI functions including feeding. This review will summarize the role of major CNS centers to gut-related inputs in the regulation of gastric function with specific reference to the regulation of food intake. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Gastrointestinal Contributions to the Postprandial Experience
Nutrients 2021, 13(3), 893; https://doi.org/10.3390/nu13030893 - 10 Mar 2021
Cited by 1 | Viewed by 770
Abstract
Food ingestion induces homeostatic sensations (satiety, fullness) with a hedonic dimension (satisfaction, changes in mood) that characterize the postprandial experience. Both types of sensation are secondary to intraluminal stimuli produced by the food itself, as well as to the activity of the digestive [...] Read more.
Food ingestion induces homeostatic sensations (satiety, fullness) with a hedonic dimension (satisfaction, changes in mood) that characterize the postprandial experience. Both types of sensation are secondary to intraluminal stimuli produced by the food itself, as well as to the activity of the digestive tract. Postprandial sensations also depend on the nutrient composition of the meal and on colonic fermentation of non-absorbed residues. Gastrointestinal function and the sensitivity of the digestive tract, i.e., perception of gut stimuli, are determined by inherent individual factors, e.g., sex, and can be modulated by different conditioning mechanisms. This narrative review examines the factors that determine perception of digestive stimuli and the postprandial experience. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Nutrient-Induced Cellular Mechanisms of Gut Hormone Secretion
Nutrients 2021, 13(3), 883; https://doi.org/10.3390/nu13030883 - 09 Mar 2021
Cited by 5 | Viewed by 1221
Abstract
The gastrointestinal tract can assess the nutrient composition of ingested food. The nutrient-sensing mechanisms in specialised epithelial cells lining the gastrointestinal tract, the enteroendocrine cells, trigger the release of gut hormones that provide important local and central feedback signals to regulate nutrient utilisation [...] Read more.
The gastrointestinal tract can assess the nutrient composition of ingested food. The nutrient-sensing mechanisms in specialised epithelial cells lining the gastrointestinal tract, the enteroendocrine cells, trigger the release of gut hormones that provide important local and central feedback signals to regulate nutrient utilisation and feeding behaviour. The evidence for nutrient-stimulated secretion of two of the most studied gut hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), along with the known cellular mechanisms in enteroendocrine cells recruited by nutrients, will be the focus of this review. The mechanisms involved range from electrogenic transporters, ion channel modulation and nutrient-activated G-protein coupled receptors that converge on the release machinery controlling hormone secretion. Elucidation of these mechanisms will provide much needed insight into postprandial physiology and identify tractable dietary approaches to potentially manage nutrition and satiety by altering the secreted gut hormone profile. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Gastrointestinal Vagal Afferents and Food Intake: Relevance of Circadian Rhythms
Nutrients 2021, 13(3), 844; https://doi.org/10.3390/nu13030844 - 05 Mar 2021
Cited by 2 | Viewed by 1111
Abstract
Gastrointestinal vagal afferents (VAs) play an important role in food intake regulation, providing the brain with information on the amount and nutrient composition of a meal. This is processed, eventually leading to meal termination. The response of gastric VAs, to food-related stimuli, is [...] Read more.
Gastrointestinal vagal afferents (VAs) play an important role in food intake regulation, providing the brain with information on the amount and nutrient composition of a meal. This is processed, eventually leading to meal termination. The response of gastric VAs, to food-related stimuli, is under circadian control and fluctuates depending on the time of day. These rhythms are highly correlated with meal size, with a nadir in VA sensitivity and increase in meal size during the dark phase and a peak in sensitivity and decrease in meal size during the light phase in mice. These rhythms are disrupted in diet-induced obesity and simulated shift work conditions and associated with disrupted food intake patterns. In diet-induced obesity the dampened responses during the light phase are not simply reversed by reverting back to a normal diet. However, time restricted feeding prevents loss of diurnal rhythms in VA signalling in high fat diet-fed mice and, therefore, provides a potential strategy to reset diurnal rhythms in VA signalling to a pre-obese phenotype. This review discusses the role of the circadian system in the regulation of gastrointestinal VA signals and the impact of factors, such as diet-induced obesity and shift work, on these rhythms. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?
Nutrients 2021, 13(3), 762; https://doi.org/10.3390/nu13030762 - 26 Feb 2021
Cited by 5 | Viewed by 1163
Abstract
Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative [...] Read more.
Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy—the two most commonly performed bariatric procedures—and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9–39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Macronutrient Sensing in the Oral Cavity and Gastrointestinal Tract: Alimentary Tastes
Nutrients 2021, 13(2), 667; https://doi.org/10.3390/nu13020667 - 19 Feb 2021
Cited by 3 | Viewed by 1318
Abstract
There are numerous and diverse factors enabling the overconsumption of foods, with the sense of taste being one of these factors. There are four well established basic tastes: sweet, sour, salty, and bitter; all with perceptual independence, salience, and hedonic responses to encourage [...] Read more.
There are numerous and diverse factors enabling the overconsumption of foods, with the sense of taste being one of these factors. There are four well established basic tastes: sweet, sour, salty, and bitter; all with perceptual independence, salience, and hedonic responses to encourage or discourage consumption. More recently, additional tastes have been added to the basic taste list including umami and fat, but they lack the perceptual independence and salience of the basics. There is also emerging evidence of taste responses to kokumi and carbohydrate. One interesting aspect is the link with the new and emerging tastes to macronutrients, with each macronutrient having two distinct perceptual qualities that, perhaps in combination, provide a holistic perception for each macronutrient: fat has fat taste and mouthfeel; protein has umami and kokumi; carbohydrate has sweet and carbohydrate tastes. These new tastes can be sensed in the oral cavity, but they have more influence post- than pre-ingestion. Umami, fat, kokumi, and carbohydrate tastes have been suggested as an independent category named alimentary. This narrative review will present and discuss evidence for macronutrient sensing throughout the alimentary canal and evidence of how each of the alimentary tastes may influence the consumption of foods. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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Review
Vagally Mediated Gut-Brain Relationships in Appetite Control-Insights from Porcine Studies
Nutrients 2021, 13(2), 467; https://doi.org/10.3390/nu13020467 - 30 Jan 2021
Cited by 2 | Viewed by 1176
Abstract
Signals arising from the upper part of the gut are essential for the regulation of food intake, particularly satiation. This information is supplied to the brain partly by vagal nervous afferents. The porcine model, because of its sizeable gyrencephalic brain, omnivorous regimen, and [...] Read more.
Signals arising from the upper part of the gut are essential for the regulation of food intake, particularly satiation. This information is supplied to the brain partly by vagal nervous afferents. The porcine model, because of its sizeable gyrencephalic brain, omnivorous regimen, and comparative anatomy of the proximal part of the gut to that of humans, has provided several important insights relating to the relevance of vagally mediated gut-brain relationships to the regulation of food intake. Furthermore, its large size combined with the capacity to become obese while overeating a western diet makes it a pivotal addition to existing murine models, especially for translational studies relating to obesity. How gastric, proximal intestinal, and portal information relating to meal arrival and transit are encoded by vagal afferents and their further processing by primary and secondary brain projections are reviewed. Their peripheral and central plasticities in the context of obesity are emphasized. We also present recent insights derived from chronic stimulation of the abdominal vagi with specific reference to the modulation of mesolimbic structures and their role in the restoration of insulin sensitivity in the obese miniature pig model. Full article
(This article belongs to the Special Issue Appetite and Satiety Control-Gut Mechanisms)
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