Gut-Brain Cross-Talk in Metabolic Control.

Because human energy metabolism evolved to favor adiposity over leanness, the availability of palatable, easily attainable, and calorically dense foods has led to unprecedented levels of obesity and its associated metabolic co-morbidities that appear resistant to traditional lifestyle interventions. However, recent progress identifying the molecular signaling pathways through which the brain and the gastrointestinal system communicate to govern energy homeostasis, combined with emerging insights on the molecular mechanisms underlying successful bariatric surgery, gives reason to be optimistic that novel precision medicines that mimic, enhance, and/or modulate gut-brain signaling can have unprecedented potential for stopping the obesity and type 2 diabetes pandemics.

Viscerosensory signalling to the nucleus accumbens via the solitary tract nucleus.

The nucleus of the solitary tract (NTS) receives direct viscerosensory vagal afferent input that drives autonomic reflexes, neuroendocrine function and modulates behaviour. A subpopulation of NTS neurons project to the nucleus accumbens (NAc); however, the function of this NTS-NAc pathway remains unknown. A combination of neuroanatomical tracing, slice electrophysiology and fibre photometry was used in mice and/or rats to determine how NTS-NAc neurons fit within the viscerosensory network. NTS-NAc projection neurons are predominantly located in the medial and caudal portions of the NTS with 54 ± 7% (mice) and 65 ± 3% (rat) being TH-positive, representing the A2 NTS cell group. In horizontal brainstem slices, solitary tract (ST) stimulation evoked excitatory post-synaptic currents (EPSCs) in NTS-NAc projection neurons. The majority (75%) received low-jitter, zero-failure EPSCs characteristic of monosynaptic ST afferent input that identifies them as second order to primary sensory neurons. We then examined whether NTS-NAc neurons respond to cholecystokinin (CCK, 20 µg/kg ip) in vivo in both mice and rats. Surprisingly, there was no difference in the number of activated NTS-NAc cells between CCK and saline-treated mice. In rats, just 6% of NTS-NAc cells were recruited by CCK. As NTS TH neurons are the primary source for NAc noradrenaline, we measured noradrenaline release in the NAc and showed that NAc noradrenaline levels declined in response to cue-induced reward retrieval but not foot shock. Combined, these findings suggest that high-fidelity afferent information from viscerosensory afferents reaches the NAc. These signals are likely unrelated to CCK-sensitive vagal afferents but could interact with other sensory and higher order inputs to modulate learned appetitive behaviours.

Deciphering the dual nature of nesfatin-1: a tale of zinc ion's Janus-faced influence.

BACKGROUND: Nucleobindin-2 (Nucb2) and nesfatin-1 (N1) are widely distributed hormones that regulate numerous physiological processes, from energy homeostasis to carcinogenesis. However, the role of nesfatin-2 (N2), the second product of Nucb2 proteolytic processing, remains elusive. To elucidate the relationship between the structure and function of nesfatins, we investigated the properties of chicken and human homologs of N1, as well as a fragment of Nucb2 consisting of N1 and N2 conjoined in a head-to-tail manner (N1/2). RESULTS: Our findings indicate that Zn(II) sensing, in the case of N1, is conserved between chicken and human species. However, the data presented here reveal significant differences in the molecular features of the analyzed peptides, particularly in the presence of Zn(II). We demonstrated that Zn(II) has a Janus effect on the M30 region (a crucial anorexigenic core) of N1 and N1/2. In N1 homologs, Zn(II) binding results in the concealment of the M30 region driven by a disorder-to-order transition and adoption of the amyloid fold. In contrast, in N1/2 molecules, Zn(II) binding causes the exposure of the M30 region and its destabilization, resulting in strong exposure of the region recognized by prohormone convertases within the N1/2 molecule. CONCLUSIONS: In conclusion, we found that Zn(II) binding is conserved between chicken and human N1. However, despite the high homology of chicken and human N1, their interaction modes with Zn(II) appear to differ. Furthermore, Zn(II) binding might be essential for regulating the function of nesfatins by spatiotemporally hindering the N1 anorexigenic M30 core and concomitantly facilitating N1 release from Nucb2.

Low dose of propyl-pyrazole-triol, an agonist of estrogen receptor alpha, administration stimulates the Coolidge effect in fadrozole-treated male rats.

Estrogen receptor (ER) α is involved in male sexual function. Here, we aim to investigate how ERα activation influences sexual satiety and the Coolidge effect (i.e., when a rat, that has reached sexual satiety, experiences an increased arousal after exposure to a novel sexual partner) in estrogen-deprived male rats. Male rats (8 per group) were treated daily for 29 days with either saline (Control group) or fadrozole dissolved in saline (1 mg/kg/day) 1 h before mating. On Days 13 and 29, rats treated with fadrozole received either no additional treatment (fadrozole group) or a single injection of propyl-pyrazole-triol (ERα-agonist group, dissolved in sesame oil, 1 mg/kg). Rats mated until reaching sexual satiety on Days 13 and 29. In these sessions, the Control group displayed higher frequency of intromission and ejaculation than the other groups. The ERα-agonist group mounted more frequently but reached sexual satiety sooner than the Control group. On Day 29, when exposed to a new sexual partner, the fadrozole-treated rats were less likely to display intromission than the other groups, or ejaculation than the Control group, or mounting than the ERα-agonist group. The Control group showed more ejaculatory behavior and shorter ejaculation latency than the other groups. Body weights, testosterone levels, estradiol levels, and ERα-immunoreactive cell counts in brain regions for sexual behavior were comparable between groups after 29 days of treatments. Our data suggest that estrogen helps regulate sexual satiety and the Coolidge effect in male rats.

How did the use of the social marketing approach in Egyptian communities succeed in improving breastfeeding practices and infants' growth?

INTRODUCTION: Improving breastfeeding practices does not always link to interventions relying only on improving nutrition awareness and education but needs cultural and behavioral insights . AIM: This study aimed to evaluate the changes in core breastfeeding indicators as a result of the use of social marketing (SM) approach for improving breastfeeding practices of Egyptian women and the physical growth of infants aged 6 to 12 months. The core breastfeeding indicators were: Early initiation of breastfeeding within one hour of birth, Predominant and exclusive breastfeeding to 6 months (EBF), Bottle feeding with formula, continued breastfeeding to 1 and 2 years, and responsiveness to cues of hunger and satiety. METHODS: A quasi-experimental longitudinal study with a posttest-only control design was done over 3 years in three phases; the first was in-depth interviews and formative research followed by health education and counseling interventions and ended by measuring the outcome. Motivating mothers' voluntary behaviors toward breastfeeding promotion "feeding your baby like a baby" was done using SM principles: product, price, place, and promotion. The interventions targeted 646 pregnant women in their last trimester and delivered mothers and 1454 women in their childbearing period. The statistical analysis was done by using SPSS program, version 26. RESULTS: Most mothers showed significantly increased awareness about the benefits of breastfeeding and became interested in breastfeeding their children outside the house using the breastfeeding cover (Gawn) (p < 0.05). Breastfeeding initiation, exclusive breastfeeding under 6 months, frequency of breastfeeding per day, and percentage of children who continued breastfeeding till 2 years, were significantly increased (from 30%, 23%, 56%, and 32% to 62%, 47.3%, 69%, and 43.5% respectively). The girls who recorded underweight results over boys during the first year of life were significantly improved (p < 0.01) after the intervention (from 52.1% to 18.8% respectively). At the same time, girls found to be obese before the intervention (15.6%) became no longer obese. CONCLUSIONS: Improvement for the majority of the key breastfeeding indicators and physical growth of infants indicates that raising a healthy generation should start by promoting breastfeeding practices that are respectable to societal norms.

Does social-norm messaging influence expected satiety and ideal portion-size selection?

A person's perception of how long a food will stave off hunger (expected satiety) and the ideal amount to consume (ideal portion size) are both influenced by food-to-mealtime norms. Here, we examine whether social norms can modulate this effect, in three experimental studies. In study 1 (n = 235) participants were exposed to a social norm suggesting most people enjoyed consuming pasta for breakfast. There was a main effect of food-to-mealtime congruence for expected satiety and ideal portion size (p < 0.001) - participants selected a smaller portion of pasta for breakfast (vs. lunch) - but there were no other main effects/interactions (p ≥ 0.15). Study 2 (n = 200) followed the same approach as study 1, but sought to examine whether the typical volume of food consumed at breakfast and lunch needed to be controlled. Again, there was a main effect of congruence (the same pattern) (p ≤ 0.02) but no other main effects/interactions (p ≥ 0.73). Study 3 (n = 208) followed the same approach as study 2, but the social-norm message was changed to suggest that most people who eat pasta for breakfast found it effectively reduced their hunger. Again, there was a main effect of congruence (the same pattern) (p < 0.001) but no other main effects/interaction (p ≥ 0.26). These studies provide further evidence for the food-to-mealtime effect, but do not provide any evidence that a single, simple social-norm statement can modulate expected satiety or ideal portion size, or interact with the food-to-mealtime effect.

Augmented gut hormone response to feeding in older adults exhibiting low appetite.

Age-related changes in gut hormones may play a role in anorexia of ageing. The aim of this study was to determine concentrations of ghrelin, PYY, and GLP-1 in older adults exhibiting an anorexia of ageing phenotype. Thirteen older adults with healthy appetite (OA-HA; 8f, 75 ± 7 years, 26.0 ± 3.2 kg m-2), fifteen older adults with low appetite (OA-LA; 10f, 72 ± 7 years, 23.6 ± 3.1 kg m-2), and twelve young adults (YA; 6f, 22 ± 2 years, 24.4 ± 2.0 kg m-2) completed the study. Healthy appetite and low appetite were determined based on BMI, habitual energy intake, self-reported appetite, and laboratory-assessed ad libitum lunch intake. Participants provided a fasted measure of subjective appetite and blood sample (0 min) before consuming a standardised breakfast (450 kcal). Appetite was measured and blood samples were drawn throughout a 240-min rest period. At 240 min, an ad libitum lunch meal was consumed. Relative intake at lunch (expressed as percentage of estimated total energy requirement) was lower for OA-LA (19.8 ± 7.7%) than YA (41.5 ± 9.2%, p < 0.001) and OA-HA (37.3 ± 10.0%, p < 0.001). Ghrelin suppression was greater for OA-LA (net AUC, -78719 ± 74788 pg mL-1·240min-1) than both YA (-23899 ± 27733 pg mL-1·240min-1, p = 0.016) and OA-HA (-21144 ± 31161 pg mL-1·240min-1, p = 0.009). There were trends for higher GLP-1 concentrations in OA-LA compared with YA at 90 min (8.85 ± 10.4 pM vs. 1.88 ± 4.63 pM, p = 0.073) and 180 min (5.00 ± 4.71 pM vs. 1.07 ± 2.83 pM, p = 0.065). There was a trend for a greater PYY response for OA-LA compared with OA-HA (net AUC p = 0.062). "Anorexigenic response score" - a composite score of gut hormone responses to feeding - showed greater anorexigenic response in OA-LA, compared with YA and OA-HA. No differences were seen in subjective appetite. These observations suggest augmented anorexigenic responses of gut hormones to feeding may be causal mechanisms of anorexia of ageing.

Appetite, food intake, and gut hormone responses to glycomacropeptide protein ingestion in older adults: A feasibility, acceptability, and pilot study.

Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.

Independent effects of volume and energy density manipulation on energy intake and appetite in healthy adults: A randomized, controlled, crossover study.

Consuming enough energy to meet high energy demands can be challenging for military personnel wherein logistical constraints limit food availability. Increasing dietary energy density (ED) and/or volume density (VD) of rations may be countermeasures, but whether positive linear associations between ED and energy intake (EI) hold at moderate-to-high ED and VD is unclear. This study examined the effects of covertly increasing the ED and VD of moderate ED (≥1.6 kcal/g) foods on appetite and energy intake. Twenty healthy men completed four 2-day treatments in random order by consuming a standardized diet containing three experimental food items (EXP) engineered using leavening, physical compression and fat manipulation to be isovolumetric but lower (L) or higher (H) in ED and VD creating four treatments: LED/LVD, LED/HVD, HED/LVD, HED/HVD. Consumption of EXP was compulsory during two meals and a snack, but remaining intake was self-selected (SSF). Results failed to show any ED-by-VD interactions. During LVD, EI was lower for EXP (-417 kcal [95%CI: 432, -402], p < 0.01) and TOTAL (SSF + EXP) (-276 kcal [95%CI: 470, -83], p = 0.01) compared to HVD, while SSF EI did not differ (140 kcal [-51, 332], p = 0.15). During LED, EI for EXP (-291 kcal [95%CI: 306, -276], p < 0.01) was lower than HED, while SSF EI was higher than HED (203 kcal 95%CI: [12, 394], p = 0.04) and TOTAL EI did not differ (-88 kcal [-282, 105], p = 0.36). Thus, when a small isovolumetric portion of the diet was manipulated, increasing the VD of moderate ED foods failed to elicit compensatory reductions in ad libitum EI while increasing the ED of moderate ED foods did. Findings may support VD manipulation of moderate ED foods as a strategy to promote increased short-term EI in environments wherein logistical burden may limit food volume.

Evidence that carbohydrate-to-fat ratio and taste, but not energy density or NOVA level of processing, are determinants of food liking and food reward.

This virtual (online) study tested the common but largely untested assumptions that food energy density, level of processing (NOVA categories), and carbohydrate-to-fat (CF) ratio are key determinants of food reward. Individual participants (224 women and men, mean age 35 y, 53% with healthy weight, 43% with overweight or obesity) were randomised to one of three, within-subjects, study arms: energy density (32 foods), or level of processing (24 foods), or CF ratio (24 foods). They rated the foods for taste pleasantness (liking), desire to eat (food reward), and sweetness, saltiness, and flavour intensity (for analysis averaged as taste intensity). Against our hypotheses, there was not a positive relationship between liking or food reward and either energy density or level of processing. As hypothesised, foods combining more equal energy amounts of carbohydrate and fat (combo foods), and foods tasting more intense, scored higher on both liking and food reward. Further results were that CF ratio, taste intensity, and food fibre content (negatively), independent of energy density, accounted for 56% and 43% of the variance in liking and food reward, respectively. We interpret the results for CF ratio and fibre in terms of food energy-to-satiety ratio (ESR), where ESR for combo foods is high, and ESR for high-fibre foods is low. We suggest that the metric of ESR should be considered when designing future studies of effects of food composition on food reward, preference, and intake.

Nutrient clustering, NOVA classification, and nutrient profiling: How do they overlap, and what do they predict about food palatability?

We compared the performance of three food categorisation metrics in predicting palatability (taste pleasantness) using a dataset of 52 foods, each rated virtually (online) by 72-224 participants familiar with the foods in question, as described in Appetite 193 (2024) 107124. The metrics were nutrient clustering, NOVA, and nutrient profiling. The first two of these metrics were developed to identify, respectively: 'hyper-palatable' foods (HPFs); and ultra-processed foods (UPFs), which are claimed to be 'made to be hyper-palatable'. The third metric categorises foods as high fat, sugar, salt (HFSS) foods versus non-HFSS foods. There were overlaps, but also significant differences, in categorisation of the foods by the three metrics: of the 52 foods, 35 (67%) were categorised as HPF, and/or UPF, and/or HFSS, and 17 (33%) were categorised as none of these. There was no significant difference in measured palatability between HPFs and non-HPFs, nor between UPFs and non-UPFs (p ≥ 0.412). HFSS foods were significantly more palatable than non-HFSS foods (p = 0.049). None of the metrics significantly predicted food reward (desire to eat). These results do not support the use of hypothetical combinations of food ingredients as proxies for palatability, as done explicitly by the nutrient clustering and NOVA metrics. To discover what aspects of food composition predict palatability requires measuring the palatability of a wide range of foods that differ in composition, as we do here.

Visceral sensitivity, hunger responsiveness, and satiety responsiveness: Associations between facets of gastrointestinal interoception and disordered eating profiles in an undergraduate sample.

This preregistered study examined associations between empirically derived profiles of disordered eating in a diverse nonclinical sample and three facets of gastrointestinal (GI) interoception (visceral sensitivity, hunger responsiveness, satiety responsiveness). University students (n = 591; 53.3% women; 23.0% Hispanic) completed the Visceral Sensitivity Index, Adult Eating Behavior Questionnaire, and Eating Pathology Symptom Inventory. Latent profile analysis was conducted in Mplus v8.3 with four behavioral indicators (restricting, binge eating, excessive exercise, purging [binary]). Facets of GI interoception predicting odds of disordered eating profile membership compared to an asymptomatic group were evaluated. Five profiles were identified. Facets of GI interoception differentially predicted odds of membership in disordered eating profiles. However, higher scores on all three facets of GI interoception were associated with increased odds of membership in a high disordered eating profile. The relationship between distinct facets of GI interoception and specific disordered eating patterns appears nuanced, though individuals displaying a range of disordered eating behaviors may exhibit broad GI interoceptive dysfunction. Findings are consistent with the recent emphasis on idiographic treatment approaches for disordered eating and may have implications for screening among university students. Prospective longitudinal work and extension to clinical samples is needed.

Abnormal functional connectivity of the reward circuit associated with early satiety in patients with postprandial distress syndrome.

Postprandial distress syndrome (PDS) is the most common functional dyspepsia (FD) subtype. Early satiety is one of the cardinal symptoms of the PDS subtype in FD patients. The heterogeneity of symptoms in FD patients hampered therapy for patients based on specific symptoms, necessitating a symptom-based understanding of the pathophysiology of FD. To investigate the correlation between reward circuit and symptom severity of PDS patients, seed (Nucleus accumbens, NAc, a key node in the reward circuit) based resting-state functional connectivity (FC) was applied in the neuroimaging data analysis. The results demonstrated that the patients with PDS manifested strengthened FC between NAc and the caudate, putamen, pallidum, amygdala, hippocampus, thalamus, anterior cingulate cortex (ACC), and insula. Moreover, the FC between NAc and ACC, insula, thalamus, and hippocampus exhibited significant positive associations with symptom severity. More importantly, the strengthened FC between NAc and the ACC, insula, amygdala, and hippocampus were found associated with the early satiety symptom of patients with PDS. This study indicated that the altered FC of reward circuit regions may play a role in the pathophysiology of patients with PDS, and some of the aberrant NAc-based FC within the reward circuit were more related to the early satiety of patients with PDS. These findings improve our symptom-based understanding of the central pathophysiology of FD, lay the groundwork for an objective diagnosis of FD, and shed light on the precise prescription for treating FD based on symptoms.

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

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

Slc12a2 loss in insulin-secreting ß-cells links development of overweight and metabolic dysregulation to impaired satiation control of feeding.

Male mice lacking the Na+-K+-2Cl- cotransporter Slc12a2 (Nkcc1) specifically in insulin-secreting ß-cells (Slc12a2ßKO) have reduced ß-cell mass and mild ß-cell secretory dysfunction associated with overweight, glucose intolerance, insulin resistance, and metabolic abnormalities. Here, we confirmed and extended previous results to female Slc12a2ßKO mice, which developed a similar metabolic syndrome-like phenotype as males, albeit milder. Notably, male and female Slc12a2ßKO mice developed overweight without consuming excess calories. Analysis of the feeding microstructure revealed that young lean Slc12a2ßKO male mice ate meals of higher caloric content and at a relatively lower frequency than normal mice, particularly during the night. In addition, overweight Slc12a2ßKO mice consumed significantly larger meals than lean mice. Therefore, the reduced satiation control of feeding precedes the onset of overweight and is worsened in older Slc12a2ßKO mice. However, the time spent between meals remained intact in lean and overweight Slc12a2ßKO mice, indicating conserved satiety responses to ad libitum feeding. Nevertheless, satiety was intensified during and after refeeding only in overweight males. In lean females, satiety responses to refeeding were delayed relative to age- and body weight-matched control mice but normalized in overweight mice. Since meal size did not change during refeeding, these data suggested that the satiety control of eating after fasting is impaired in lean Slc12a2ßKO mice before the onset of overweight and independently of their reduced satiation responses. Therefore, our results support the novel hypothesis that reduced satiation precedes the onset of overweight and the development of metabolic dysregulation.NEW & NOTEWORTHY Obesity, defined as excess fat accumulation, increases the absolute risk for metabolic diseases. Although obesity is usually attributed to increased food intake, we demonstrate that body weight gain can be hastened without consuming excess calories. In fact, impaired meal termination control, i.e., satiation, is detectable before the development of overweight in an animal model that develops a metabolic syndrome-like phenotype.

Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis.

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD0)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD0 and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis underwent GES to obtain gastric retention and IMD0, WLST, and filled out patient assessment of upper GI symptoms. A total of 234 patients with symptoms of gastroparesis were assessed (86 patients with diabetes, 130 idiopathic, 18 postfundoplication) and 175 (75%) delayed gastric emptying. Low IMD0 <0.568 suggesting initial rapid transit to the distal stomach was present in 8% and correlated with lower gastric retention, less heartburn, and lower volumes consumed during WLST. Low WLST volume (<238 mL) was present in 20% and associated with increased severity of early satiety, postprandial fullness, loss of appetite, and nausea. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. Thus, IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.NEW & NOTEWORTHY IMD0 and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.

The effect of hunger state on hypothalamic functional connectivity in response to food cues.

The neural underpinnings of the integration of internal and external cues that reflect nutritional status are poorly understood in humans. The hypothalamus is a key integrative area involved in short- and long-term energy intake regulation. Hence, we examined the effect of hunger state on the hypothalamus network using functional magnetic resonance imaging. In a multicenter study, participants performed a food cue viewing task either fasted or sated on two separate days. We evaluated hypothalamic functional connectivity (FC) using psychophysiological interactions during high versus low caloric food cue viewing in 107 adults (divided into four groups based on age and body mass index [BMI]; age range 24-76 years; BMI range 19.5-41.5 kg/m2 ). In the sated compared to the fasted condition, the hypothalamus showed significantly higher FC with the bilateral caudate, the left insula and parts of the left inferior frontal cortex. Interestingly, we observed a significant interaction between hunger state and BMI group in the dorsolateral prefrontal cortex (DLPFC). Participants with normal weight compared to overweight and obesity showed higher FC between the hypothalamus and DLPFC in the fasted condition. The current study showed that task-based FC of the hypothalamus can be modulated by internal (hunger state) and external cues (i.e., food cues with varying caloric content) with a general enhanced communication in the sated state and obesity-associated differences in hypothalamus to DLPFC communication. This could potentially promote overeating in persons with obesity.

Prelimbic cortex inactivation prevents ABA renewal based on satiety state.

We have previously shown that the rat prelimbic cortex (PL) is necessary for contexts to promote the performance of instrumental behaviors that have been learned in them, whether the context is physical (operant chamber) or behavioral (recent performance of a behavior that has historically preceded the target in a behavior chain). In the present experiment, we investigated the role of the PL in satiety level as an interoceptive acquisition context. Rats were trained to lever-press for sweet/fat pellets while sated (22 hrs continuous food access) followed by the extinction of the response while hungry (22 hrs food deprived). Pharmacological inactivation of the PL (with baclofen/muscimol infusion) attenuated renewal of the response that occurred upon a return to the sated context. In contrast, animals that received a vehicle (saline) infusion showed renewal of the previously extinguished response. These results support the hypothesis that the PL monitors the relevant contextual elements (physical, behavioral, or satiety state) associated with reinforcement of a response and promotes the subsequent performance of that response in their presence.

Protein Source Influences Acute Appetite and Satiety but Not Subsequent Food Intake in Healthy Adults.

BACKGROUND: Although current recommendations encourage plant-based dietary patterns, data is limited as to whether the equivalent substitution of animal-based protein-rich foods with plant-based versions impacts ingestive behavior. OBJECTIVES: To compare higher-protein preloads, varying in protein source, on appetite, satiety, and subsequent energy intake. METHODS: Thirty-two adults (age: 25 ± 1 y; body mass index (BMI) measured in kg/m2: 24.2 ± 0.5 kg/m2) randomly consumed 250 kcal, protein-preload beverages (24 g protein), varying in protein source [whey, soy, and pea protein isolates (WHEY, SOY, and PEA) or micellar casein (CAS)] each morning for 3 acclimation days/preload. On day 4, participants completed a 4-h clinical testing day in which the respective preload was consumed, followed by blood sampling and questionnaires every 30 min for appetite and satiety. In addition, an ad libitum lunch was provided 4-h postpreload. On day 5, participants consumed the respective preload at home, followed by an ad libitum breakfast 30 min afterward. For normally-distributed data, repeated-measures analysis of variance (ANOVA) or Friedman nonparametric test were utilized to compare the main effects of protein source on study outcomes. Post hoc pairwise comparisons using least-significant differences (LSD) were then performed. RESULTS: CAS (-3330 ± 690 mm∗240 min) and PEA (-2840 ± 930mm∗240 min) reduced 4-h appetite compared with SOY (-1440 ± 936 mm∗240 min; both, P < 0.05). WHEY was not different (-2290 ± 930 mm∗240 min). CAS (3520 ± 84 pg/mL∗240 min) and PEA (3860 ± 864 pg/mL∗240 min) increased 4-h peptide YY concentrations compared with SOY (2200 ± 869 pg/mL∗240 min; both, P < 0.05). WHEY was not different (3870 ± 932 pg/mL∗240 min). No differences in ad libitum energy intake were observed. CONCLUSIONS: CAS and PEA, but not WHEY, elicited greater acute changes in appetite and satiety compared with SOY in healthy adults, supporting that not all protein sources are equivalent. This trial is registered at clinicaltrials.gov (NCT03154606).

Glycomacropeptide Impacts Amylin-Mediated Satiety, Postprandial Markers of Glucose Homeostasis, and the Fecal Microbiome in Obese Postmenopausal Women.

BACKGROUND: Obesity with metabolic syndrome is highly prevalent and shortens lifespan. OBJECTIVES: In a dose-finding crossover study, we evaluated the effect of glycomacropeptide (GMP) on satiety, glucose homeostasis, amino acid concentrations, inflammation, and the fecal microbiome in 13 obese women. METHODS: Eligible women were ≤10 yr past menopause with a body mass index [BMI (in kg/m2)] of 28 to 35 and no underlying inflammatory condition affecting study outcomes. Participants consumed GMP supplements (15 g GMP + 10 g whey protein) twice daily for 1 wk and thrice daily for 1 wk, with a washout period between the 2 wk. Women completed a meal tolerance test (MTT) on day 1 (soy MTT) and day 7 (GMP MTT) of each week. During each test, subjects underwent measures of glucose homeostasis, satiety, cytokines, and the fecal microbiome compared with that of usual diet, and rated the acceptability of consuming GMP supplements. RESULTS: The mean ± SE age of the 13 women was 57 ± 1 yr, with a median of 8 yr (range: 3-9 yr) past menopause and a BMI of 30 (IQR: 29-32). GMP was highly acceptable to participants, permitting high adherence. Metabolic effects were similar for twice or thrice daily GMP supplementation. Glucose, insulin, and cytokine concentrations were no different. The postprandial area under the curve (AUC) for glucagon concentrations was significantly lower, and the insulin-glucagon ratio was significantly higher with GMP than that with the soy MTT. Postprandial AUC amylin concentration was significantly higher with GMP than that with the soy MTT and correlated with C-peptide (P < 0.001; R2 = 0.52) and greater satiety. Ingestion of GMP supplements twice daily reduced members of the genus Streptococcus (P = 0.009) and thrice daily consumption reduced overall α diversity. CONCLUSIONS: GMP is shown to increase amylin concentrations, improve glucose homeostasis, and alter the fecal microbiome. GMP can be a helpful nutritional supplement in obese postmenopausal women at risk for metabolic syndrome. Further investigation is warranted. This trial was registered at clinicaltrials.gov as NCT05551091.