Hunger Signals Research Articles

Day/night Changes in the Dorsomedial Hypothalamus Firing Responses to Ghrelin are Modulated by High-fat Diet

Dorsomedial hypothalamus (DMH) is a part of the feeding center involved in food intake and regulation of the metabolism. DMH neurons express many receptors for different metabolic cues which can modulate its network and influence animals’ behaviour. One of the metabolic peptides deliveredto this structure is ghrelin, the only well-known hunger signal, produced mainly in the stomach. Diet-induced obesity is a physiological model of obesity widely used in research. Here we investigated how time-of-day and high-fat diet (HFD) affect neuronal networks and the sensitivity to the metabolic information received by the DMH. Our results indicate that even a short period of HFD (2–3 weeks) consumption can cause dysregulation of the DMH neuronal network, manifested as a disruption of the day/night pattern of basal activity and altered sensitivity to incoming information. We showed for the first time a day/night pattern of sensitivity to ghrelin in the DMH, with a higher level during the behaviorally active phase of animals. This day/night rhythm of sensitivity to ghrelin was reversed in HFD group, causing a stronger effect during the non-active phase. After prolongation of the HFD consumption to 7–8 weeks we observed an increase in the responsiveness to ghrelin, than during the short-term diet.

Calorie restriction and calorie dilution have different impacts on body fat, metabolism, behavior, and hypothalamic gene expression.

Caloric restriction is a robust intervention to increase lifespan. Giving less food (calorie restriction [CR]) or allowing free access to a diluted diet with indigestible components (calorie dilution [CD]) are two methods to impose restriction. CD does not generate the same lifespan effect as CR. We compare responses of C57BL/6 mice with equivalent levels of CR and CD. The two groups have different responses in fat loss, circulating hormones, and metabolic rate. CR mice are hungrier, as assessed by behavioral assays. Although gene expression of Npy, Agrp, and Pomc do not differ between CR and CD groups, CR mice had a distinctive hypothalamic gene-expression profile with many genes related to starvation upregulated relative to CD. While both result in lower calorie intake, CR and CD are not equivalent procedures. Increased hunger under CR supports the hypothesis that hunger signaling is a key process mediating the benefits of CR.

Gastral Drumming in Vespula germanica (Hymenoptera: Vespidae): Vibrational Communication at Night Suggests Additional Roles in Colony Organization.

Gastral drumming (GD) is a type of vibrational communication that has been reported in several species of yellowjackets and hornets. Despite early claims that it acts as a hunger signal, a more recent study found evidence that it acts as a nest-based food-recruitment signal, the first reported for eusocial wasps. Early studies also claimed, without supporting data, that it is produced most often in the early morning hours when the sun rises. Here, I recorded drumming continuously in colonies of Vespula germanica (Fabricius) to assess whether production was highest in the morning. Although I found no evidence in support of greater early morning production, I found, surprisingly, that it is produced at night, a time when foraging does not occur. When these results are combined with the results from previous studies on this species and similar findings in honey bees, they suggest that GD may be a modulatory signal, which acts by increasing general activity levels and by increasing the rate that individuals come into contact with social cues.

Ghrelin deficiency sex-dependently affects food intake, locomotor activity, and adipose and hepatic gene expression in a binge-eating mouse model.

Binge-eating disorder is the most prevalent eating disorder diagnosed, affecting three times more women than men. Ghrelin stimulates appetite and reward signaling, and loss of its receptor reduces binge-eating behavior in male mice. Here, we examined the influence of ghrelin itself on binge-eating behavior in both male and female mice. Five-wk-old wild-type (WT) and ghrelin-deficient (Ghrl-/-) mice were housed individually in indirect calorimetry cages for 9 wks. Binge-like eating was induced by giving mice ad libitum chow, but time-restricted access to a Western-style diet (WD; 2 h access, 3 days/wk) in the light phase (BE); control groups received ad libitum chow (CO), or ad libitum access to both diets (CW). All groups of BE mice showed binge-eating behavior, eating up to 60% of their 24-h intake during the WD access period. Subsequent dark phase chow intake was decreased in Ghrl-/- mice and remained decreased in Ghrl-/- females on nonbinge days. Also, nonbinge day locomotor activity was lower in Ghrl-/- than in WT BE females. Upon euthanasia, Ghrl-/- BE mice weighed less and had a lower lean body mass percentage than WT BE mice. In BE and CW groups, ghrelin and sex altered the expression of genes involved in lipid processing, thermogenesis, and aging in white adipose tissue and livers. We conclude that, although ghrelin deficiency does not hamper the development of binge-like eating, it sex-dependently alters food intake timing, locomotor activity, and metabolism. These results add to the growing body of evidence that ghrelin signaling is sexually dimorphic.NEW & NOTEWORTHY Ghrelin, a peptide hormone secreted from the gut, is involved in hunger and reward signaling, which are altered in binge-eating disorder. Although sex differences have been described in both binge-eating and ghrelin signaling, this interaction has not been fully elucidated. Here, we show that ghrelin deficiency affects the behavior and metabolism of mice in a binge-like eating paradigm, and that the sex of the mice impacts the magnitude and direction of these effects.

The Effect of Mood Change and Intuitive Eating Skills on Self-Regulation of Food Intake among Undergraduate College Students

ABSTRACT Background Mood change, lack of self-regulation, and eating in the absence of hunger cues are exacerbating determinants in college weight gain; however, the association between these factors is not known. Purpose This study aimed to examine the correlation between mood change, intuitive eating, and self-regulation of food intake among college students. Methods This cross-over study included 60 undergraduate college students 19.8 ± 1.43 years old (62.1% females, 74.2% Latinx). Students had two visits, one week apart. Participants completed intuitive eating and mood questionnaires. Participants watched an emotional movie, then participated in a buffet style lunch calorie compensation trial. Food intake was measured using plate waste. Self-regulation was measured objectively using compensation indices (COMPX). Results Self-regulation was significantly affected by both mood change and intuitive eating. Gender was found to significantly impact this model; however, Body Mass Index did not seem to have a significant effect. Discussion College students who rely on physiological cues of hunger and satiety and are less affected by environmental elements, seem to be able to regulate their intake better, and maintain healthier weight. Translation to Health Education Practice Teaching students to rely on bodily signals of hunger and satiety may be an effective approach to maintaining healthy weight. A AJHE Self-Study quiz is online for this article via the SHAPE America Online Institute (SAOI) http://portal.shapeamerica.org/trn-Webinars

215 Impact of Maternal Diabetes on Neonatal Body Composition, Energy Homeostasis and Hypothalamic Salivary Gene Expression

OBJECTIVES/GOALS: Infants of diabetic mothers (IDMs) may exhibit decreased oral intake, requiring nasogastric feedings and prolonged hospitalization. We hypothesize that increased insulin exposure and resulting overgrowth in utero disrupts hypothalamic regulation of food intake, correlates to body composition and impacts feeding in IDMs. METHODS/STUDY POPULATION: Infants born at ≥ 35 weeks gestation to mothers with gestational or type II diabetes (IDM cohort), and normoglycemic mothers (control cohort) were recruited. Infants born to mothers with Type I DM or preeclampsia and with a history of intrauterine growth restriction, opioid exposure, or major congenital anomalies were excluded. Salivary expression of known hunger signaling genes 5AMP-activated protein kinase (AMPK), Neuropeptide Y receptor Y2 (NPY2R), leptin (LEP), ghrelin (GHRL), proopiomelanocortin (POMC), and adiponectin (ADIPOQ) were quantified using RT-qPCR. Body composition was assessed via skinfold measurements and compared and correlated between cohorts. Feeding outcomes were recorded. RESULTS/ANTICIPATED RESULTS: 23 infants were recruited in each cohort. POMC and AMPK were expressed by 71% and 88% of infants respectively in both cohorts. NPY2R was expressed by 79% and 83% of the diabetic cohort and normoglycemia cohort respectively, while GHRL was expressed by 75% and 79% of the diabetic cohort and normoglycemia cohort, respectively. LEP and ADIPOQ were not reliably expressed in either cohort. Infants with a higher body fat percentage were less likely to express NPY2R (OR= 0.76). There was no significant association between body fat percentage and expression of AMPK, POMC, or GHRL. Only 3 IDMs were noted by providers to exhibit poor oral intake, limiting our ability to correlate gene expression and body composition with feeding outcomes. DISCUSSION/SIGNIFICANCE: Non-invasive assessment of hunger signaling gene expression is possible through salivary analysis of AMPK, POMC, NPY2R, and GHRL. Given the paucity of IDMs with poor feeding in our study, future studies should target IDMs requiring feeding support to understand mechanisms driving aberrant feeding behavior.

Beta-Hydroxybutyrate Suppresses Hepatic Production of the Ghrelin Receptor Antagonist LEAP2.

IntroductionLiver-expressed antimicrobial peptide-2 (LEAP2) is an endogenous ghrelin receptor antagonist, which is upregulated in the fed state and downregulated during fasting. We hypothesized that the ketone body beta-hydroxybutyrate (BHB) is involved in the downregulation of LEAP2 during conditions with high circulating levels of BHB.MethodsHepatic and intestinal Leap2 expression were determined in 3 groups of mice with increasing circulating levels of BHB: prolonged fasting, prolonged ketogenic diet, and oral BHB treatment. LEAP2 levels were measured in lean and obese individuals, in human individuals following endurance exercise, and in mice after BHB treatment. Lastly, we investigated Leap2 expression in isolated murine hepatocytes challenged with BHB.ResultsWe confirmed increased circulating LEAP2 levels in individuals with obesity compared to lean individuals. The recovery period after endurance exercise was associated with increased plasma levels of BHB levels and decreased LEAP2 levels in humans. Leap2 expression was selectively decreased in the liver after fasting and after exposure to a ketogenic diet for 3 weeks. Importantly, we found that oral administration of BHB increased circulating levels of BHB in mice and decreased Leap2 expression levels and circulating LEAP2 plasma levels, as did Leap2 expression after direct exposure to BHB in isolated murine hepatocytes.ConclusionFrom our data, we suggest that LEAP2 is downregulated during different states of energy deprivation in both humans and rodents. Furthermore, we here provide evidence that the ketone body, BHB, which is highly upregulated during fasting metabolism, directly downregulates LEAP2 levels. This may be relevant in ghrelin receptor–induced hunger signaling during energy deprivation.

DOCK4 regulates ghrelin production in gastric X/A-like cells.

Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. Ghrelin also modulates neuroinflammatory and apoptotic processes. Dedicator of cytokinesis 4 (DOCK4), a guanine nucleotide exchange factor (GEF), isinvolvedinthe regulationofneuronal polarization and axon regeneration. However, the effect of DOCK4 on ghrelin production has not been explored. The expression of DOCK4 in human and mouse stomach was examined by immunohistochemical staining. The synthesis and secretion of ghrelin in Dock4 null mice were evaluated by real-time quantitative PCR, Western blot and ELISA. The effects of DOCK4 on ghrelin production in mHypoE-42 cells were measured by real-time quantitative PCR and Western blot. We showed that DOCK4 was expressed in both human and mouse gastric ghrelin cells. The mRNA and protein levels of gastric ghrelin, as well as ghrelin secretion, were remarkably diminished in Dock4 null mice. Furthermore, we showed that overexpression of Dock4 significantly stimulated ghrelin expression, while siRNA knockdown of endogenous Dock4 resulted in a marked decrease of ghrelin in mHypoE-N42 cells. Our results identify DOCK4 as a critical regulator for ghrelin production in gastric X/A-like cells.

Heart Rate Variability and Sympathetic Activity Is Modulated by Very Low-Calorie Ketogenic Diet.

Obesity is characterized by an energy imbalance and by the accumulation of visceral adipose tissue. The energy balance is controlled by a complex set of balanced physiological systems that provide hunger and satiety signals to the brain and regulate the body’s ability to consume energy. The central nervous system controls the metabolic state, influencing the activity of other systems and receiving information from them. Heart rate variability (HRV) is the natural variability of the heart rate in response to several factors. HRV is related to the interaction between the SNS and the parasympathetic. In the light of this evidence, the aim of this study is to investigate the possible effects of the two different dietary regimens such as very low-calorie ketogenic diet (VLCKD) vs. low caloric diet (LCD), on the functions of the nervous system, with particular attention to the autonomous control of heart rate variability (HRV). A total of 26 obese subjects underwent diet therapy in order to reduce body weight; they were also randomly divided into two groups: the VLCKD group and the LCD group. Our results showed that in both groups, there is a reduction in heart rate as an indicator of sympathetic activity; we found a statistically significant variation only in the VLCKD group. Therefore, this study supports the notion that the sympathovagal balance can be modulated by a specific diet, but further studies are needed to clarify the molecular pathway undergoing this modulation.

Responsive feeding values and practices among families across the Canadian Maritime provinces.

Children benefit from responsive feeding practices where their internal signals of hunger and satiety are valued and met with prompt, emotionally supportive, and developmentally appropriate responses. Using an online survey, this study describes responsive feeding values and practices among parents of young children (0-5 years) (n = 1039) across 3 Canadian Maritime provinces. Independent-samples t-tests and 1-way ANOVA were performed to determine the differences in survey questions related to the responsive feeding practices and values. First-time parents and parents with younger children report implementing more consistently some of the challenging responsive feeding practices, such as avoiding pressuring their children to eat, compared with parents with multiple children and parents with children ages 3-5 years. Parents often have well-intended reasons to encourage their children to eat; however, these can coincide with non-responsive practices with food such as pressuring, rewarding, and restriction. These coercive practices may be ineffective and counterproductive as they reinforce reasons to eat unrelated to appetite and self-regulation. Preschool and early feeding interventions that support parents in understanding normal child development, including typical eating behaviours and self-regulation, could help to equip them for challenging feeding experiences and encourage long-term responsive feeding practices. Novelty: First-time parents and parents with younger children report more consistently avoiding pressuring their children to eat, compared with parents with multiple children and parents with children ages 3-5 years. Parents often have well-intended reasons to encourage their children to eat; however, these can coincide with non-responsive practices such as pressuring, rewarding, and restriction.

Appetitive interoception, the hippocampus and western-style diet

Obesity, Type 2 diabetes and other metabolic disorders continue to pose serious challenges to human health and well-being. An important source of these challenges is the overconsumption of saturated fats and sugar, main staples of what has been called the Western-style diet (WD). The current paper describes a theoretical model and supporting evidence that links intake of a WD to interference with a specific brain substrate that underlies processing of interoceptive signals of hunger and satiety. We review findings from rats and humans that the capacity of these signals to modulate the strength of appetitive and eating behavior depends on the functional integrity of the hippocampus and the learning memory operations it performs. Important among these operations is the use of contextual information to retrieve memories that are associated with other events. Within our framework, satiety provides an interoceptive context that informs animals that food cues and appetitive behavior will not be followed by rewarding postingestive outcomes. This serves to prevent those cues and responses from retrieving those reward memories. The findings reviewed provide evidence that consuming a WD and the high amounts of saturated fat and sugar it contains (a) is associated with the emergence of pathophysiologies to which the hippocampus appears selectively vulnerable (b) impairs hippocampal-dependent learning and memory (HDLM) and (c) weakens behavioral control by interoceptive hunger and satiety contextual stimuli. It is hypothesized that these consequences of WD intake may establish the conditions for a vicious cycle of further WD intake, obesity, and potentially cognitive decline.

Chronic Restraint Stress Decreases the Excitability of Hypothalamic POMC Neuron and Increases Food Intake.

Stress activates the hypothalamic-pituitary-adrenal system, and induces the release of glucocorticoids, stress hormones, into circulation. Many studies have shown that stress affects feeding behavior, however, the underlying circuitry and molecular mechanisms are not fully understood. The balance between orexigenic (simulating appetite) and anorexigenic (loss of appetite) signals reciprocally modulate feeding behavior. It is suggested that proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus (ARC) of the hypothalamus are the first-order neurons that respond to the circulating signals of hunger and satiety. Here, we examined a chronic restraint stress model and observed an increase in food intake, which was not correlated with anhedonia. We investigated whether stress affects the properties of POMC and NPY neurons and found that chronic restraint stress reduced the excitatory inputs onto POMC neurons and increased the action potential threshold. Therefore, our study suggests that chronic stress modulates the intrinsic excitability and excitatory inputs in POMC neurons, leading to changes in feeding behavior.

Evaluation of the relationship of intuitive eating behaviour between body mass index and waist circumference in university students

Objective: This study was conducted to examine the relationship between intuitive eating behaviour, body mass index (BMI), and waist-hip circumference among university students. Methods: This study was conducted on 146 students studying at the Department of Nutrition and Dietetics of a foundation university on the European side of Istanbul in the 2020-2021 academic year. Socio-demographic characteristics, anthropometric measurements, and intuitive eating habits of the students were taken through an online questionnaire. Intuitive Eating Scale-2 (IES-2) was used to determine students’ intuitive eating behaviour. Results: 146 students with a mean age of 20.64±1.69 participated in the study. 62.3% of the students were female and 37.7% were male. Intuitive eating scale total score mean ± standard deviation values ​​were found to be 3.40±0.55. BMI mean ± standard deviation values were found to be 21.89 ± 3.94 kg / m2 while waist circumference mean ± standard deviation values were 69.78±9.32 cm. eating due to physical rather than emotional causes sub-dimension has a positive and significant correlation with the eating sub-dimension related to hunger and fullness signals, body-food choice congruity, and intuitive eating scale-total score. There is a significant and positive relationship between the eating sub-dimension related to hunger and fullness signals and the body-food choice congruity sub-dimension and the total score of the intuitive eating scale. A significant and positive correlation was found between the body-food choice congruity sub-dimension and the total score of the intuitive eating scale. Comparing the intuitive eating scale total scores and sub-dimensions according to BMI groups, there is a significant difference in the mean score of the body-food choice congruity sub-dimension according to the BMI classification. Conclusion: As intuitive eating increases in university students, the body mass index decreases.

Effect of Two Types of Diet on Cholecystokinin (CCK) Level in Three Groups of Males

In response to a meal, the signals of satiety suppress the signals of hunger (meaning to finish the meal). These signals originate in the pancreas and gastrointestinal tract, transmitting information from the periphery to the brain (by the vagus nerve or the circulation). The study aimed to estimate whether the serum level of Cholecystokinin (CCK) in three male groups is influenced by their type of food. The current study included Sixty volunteers of adult males (normal-weight group n=20, overweight group n=20, and obese I group n=20) (21- 24 years). The blood samples were taken from subjects in the afternoon after (30 minutes–2 hours) from lunch was consumed, during March 2021 till June 2021. ELIZA kit was used to assay the serum concentration of the Cholecystokinin hormone. The anthropometric measurements were done, such as body weight and height, to calculate body mass index (BMI) by special formula, and the subjects were assorted depending on WHO body mass index (BMI) classification. Cholecystokinin showed a significant decrease (p<0.05) in obese I (311.201±21.542) and overweight (353.494 ± 43.915) as compared with the normal weight group (646.002 ± 46.344). A significant negative correlation was noticed between the hormone and body weight. Eating palatable food leads to uncontrolled ingesting behaviors due to the shift from homeostatic to hedonic regulatory mechanisms of food intake. These changes occur primarily in individuals with obesity and thus lead to an irregularity in the secretion of anorexigenic hormones.

Contributing roles of depression, anxiety, and impulsivity dimensions in eating behaviors styles in surgery candidates

BackgroundEven if bariatric surgery is considered the most effective therapeutic approach, it is not equally successful among individuals suffering from severe obesity and candidates for this weight loss surgery. Among the factors that influence postsurgical outcomes, eating behaviors styles are known to play a key role in relapses. The aim of our study was to assess eating behaviors styles and several modulating psychopathological factors in patients suffering from severe obesity.MethodsPatients seeking bariatric surgery (N = 127) completed a set of standardized tools assessing eating behaviors (Dutch Eating Behavior Questionnaire), comorbid psychiatric conditions (Mini International Neuropsychiatric Interview), depression, and anxiety scores (Beck Depression Inventory, State-Trait Anxiety Inventory), and impulsivity scores (UPPS-P Impulsive Behavior Scale).ResultsWe detected significant correlations between DEBQ Emotional Eating (EmoE) and depression, state and trait anxiety, and all dimensions of impulsivity. Significant correlations were also present between DEBQ External Eating (ExtE) and depression, state and trait anxiety and UPPS-P positive urgency, lack of perseverance and sensation seeking. Regression analyses identified sex (female), trait anxiety, and lack of perseverance as explanatory factors for EmoE, and depression severity score and positive urgency for ExtE.ConclusionsEmoE might be a means of dealing with negative emotions and/or intrusive thoughts, while ExtE might result from a mechanism associated with depression. These results should help to improve patients’ outcomes by defining specific therapeutic targets in psychological interventions.Plain English summaryAfter bariatric surgery, some patients regain weight. This is likely due to various factors, including a return of maladaptive eating styles, such as emotional eating (which occurs as a response to negative emotions, like depression, anxiety, anger, sadness, and discouragement), external eating (which refers to the tendency to eat in response to positive external cues, regardless of internal signals of hunger and satiety), and restraint eating (implying to make efforts to develop and maintain strategies to control calories intake, associated with weight loss after lifestyle intervention). Our goal in this research project was to explore associated factors (particularly depression, anxiety, and impulsivity) to these eating styles in patients suffering from obesity prior to bariatric surgery. Individuals seeking bariatric surgery were asked questions about their eating styles and their levels of depression, anxiety, and impulsivity using standardized questionnaires. We found that emotional eating might be a means of dealing with negative emotions and/or intrusive thoughts (e.g. about food or body dissatisfaction), while external eating might result from a mechanism associated with depression. We detected no association between restraint eating and any of the dimensions of impulsivity, nor depression and anxiety. Therapies aimed at improving patients’ abilities to regulate negative affects seem promising among subjects suffering from obesity and those seeking bariatric surgery. If well learned, these therapies might also help them to maintain weight loss after surgery by limiting maladaptive eating styles.

External food cue responsiveness and emotional eating in adolescents: A multimethod study

Eating in response to external food cues (i.e., external eating) and internal emotional experiences (i.e., emotional eating) are associated with obesity. While external and emotional eating co-occur, little is known about how external food cue responsiveness may interact with internal emotional cues to influence eating episodes in adolescents. The current study examined how trait-level external food cue responsiveness modulates momentary associations between affective states and eating in adolescents. Participants were drawn from a prior study of siblings (N = 78; ages 13–17) who completed an ecological momentary assessment protocol to assess eating episodes and affective states. External food cue responsiveness was determined by comparing energy consumption following presentation of an appetizing food (pizza) on one day and a control activity (reading) on another day. Generalized linear mixed models examined positive and negative affective states, cue responsiveness, and their interactions as predictors of the likelihood of eating. The relationship between affective states and likelihood of eating was stronger among adolescents with higher versus lower external food cue responsiveness. Among adolescents with higher cue responsiveness, endorsing negative affect was associated with a lower likelihood of eating, whereas endorsing positive affect was associated with a higher likelihood of eating (within-person effects). Findings suggest that high sensitivity to external food cues and greater proclivity for emotional eating may be likely to coincide such that any cue, internal or external, is likely to disrupt sensitivity to internal hunger and satiety signals. Future studies are needed to elucidate how sensitivities to internal and external cues may interact to influence obesity risk.

SensEat: The effect of a brief mindfulness intervention on perception of bodily signals of satiation and hunger.

SensEat: The effect of a brief mindfulness intervention on perception of bodily signals of satiation and hunger.

Motilin Comparative Study: Structure, Distribution, Receptors, and Gastrointestinal Motility.

Motilin, produced in endocrine cells in the mucosa of the upper intestine, is an important regulator of gastrointestinal (GI) motility and mediates the phase III of interdigestive migrating motor complex (MMC) in the stomach of humans, dogs and house musk shrews through the specific motilin receptor (MLN-R). Motilin-induced MMC contributes to the maintenance of normal GI functions and transmits a hunger signal from the stomach to the brain. Motilin has been identified in various mammals, but the physiological roles of motilin in regulating GI motility in these mammals are well not understood due to inconsistencies between studies conducted on different species using a range of experimental conditions. Motilin orthologs have been identified in non-mammalian vertebrates, and the sequence of avian motilin is relatively close to that of mammals, but reptile, amphibian and fish motilins show distinctive different sequences. The MLN-R has also been identified in mammals and non-mammalian vertebrates, and can be divided into two main groups: mammal/bird/reptile/amphibian clade and fish clade. Almost 50 years have passed since discovery of motilin, here we reviewed the structure, distribution, receptor and the GI motility regulatory function of motilin in vertebrates from fish to mammals.

Ghrelin octanoylation by ghrelin O-acyltransferase: protein acylation impacting metabolic and neuroendocrine signalling.

The acylated peptide hormone ghrelin impacts a wide range of physiological processes but is most well known for controlling hunger and metabolic regulation. Ghrelin requires a unique posttranslational modification, serine octanoylation, to bind and activate signalling through its cognate GHS-R1a receptor. Ghrelin acylation is catalysed by ghrelin O-acyltransferase (GOAT), a member of the membrane-bound O-acyltransferase (MBOAT) enzyme family. The ghrelin/GOAT/GHS-R1a system is defined by multiple unique aspects within both protein biochemistry and endocrinology. Ghrelin serves as the only substrate for GOAT within the human proteome and, among the multiple hormones involved in energy homeostasis and metabolism such as insulin and leptin, acts as the only known hormone in circulation that directly stimulates appetite and hunger signalling. Advances in GOAT enzymology, structural modelling and inhibitor development have revolutionized our understanding of this enzyme and offered new tools for investigating ghrelin signalling at the molecular and organismal levels. In this review, we briefly summarize the current state of knowledge regarding ghrelin signalling and ghrelin/GOAT enzymology, discuss the GOAT structural model in the context of recently reported MBOAT enzyme superfamily member structures, and highlight the growing complement of GOAT inhibitors that offer options for both ghrelin signalling studies and therapeutic applications.

The gastrointestinal tract in hunger and satiety signalling.

BackgroundDifferent peripheral pathways are implicated in the regulation of the food ingestion‐digestion cycle.MethodsNarrative review on gastrointestinal mechanisms involved in satiety and hunger signalling.ResultsCombined mechano‐ and chemoreceptors, peripherally released peptide hormones and neural pathways provide feedback to the brain to determine sensations of hunger (increase energy intake) or satiation (cessation of energy intake) and regulate the human metabolism. The gastric accommodation reflex, which consists of a transient relaxation of the proximal stomach during food intake, has been identified as a major determinant of meal volume, through activation of tension‐sensitive gastric mechanoreceptors. Motilin, whose release is the trigger of gastric Phase 3, has been identified as the major determinant of return of hunger after a meal. In addition, the release of several peptide hormones such as glucagon‐like peptide 1 (GLP‐1), cholecystokinin as well as motilin and ghrelin contributes to gut‐brain signalling with relevance to control of hunger and satiety. A number of nutrients, such as bitter tastants, as well as pharmacological agents, such as endocannabinoid receptor antagonists and GLP‐1 analogues act on these pathways to influence hunger, satiation and food intake.ConclusionGastrointestinal mechanisms such as gastric accommodation and motilin release are key determinants of satiety and hunger.