The herbal preparation, STW5-II, reduces proximal gastric tone and stimulates antral pressures in healthy humans.

BACKGROUND: The herbal preparation, STW5-II, improves upper gastrointestinal symptoms, including abdominal fullness, early satiation, and epigastric pain, in patients with functional dyspepsia, and in preclinical models decreases fundic tone and increases antral contractility. The effects of STW5-II on esophago-gastric junction pressure, proximal gastric tone and antropyloroduodenal pressures, disturbances of which may contribute to symptoms associated with disorders of gut-brain interaction, including functional dyspepsia, in humans, have, hitherto, not been evaluated. METHODS: STW5-II or placebo (matched for color, aroma, and alcohol content) were each administered orally, at the recommended dose (20 drops), to healthy male and female volunteers (age: 27 ± 1 years) in a double-blind, randomized fashion, on two separate occasions, separated by 3-7 days, to evaluate effects on (i) esophago-gastric junction pressures following a standardized meal using solid-state high-resolution manometry (part 1, n = 16), (ii) proximal gastric volume using a barostat (part 2, n = 16), and (iii) antropyloroduodenal pressures assessed by high-resolution manometry (part 3, n = 18), for 120 min (part 1) or 180 min (parts 2, 3). KEY RESULTS: STW5-II increased maximum intrabag volume (ml; STW5-II: 340 ± 38, placebo: 251 ± 30; p = 0.007) and intrabag volume between t = 120 and 180 min (p = 0.011), and the motility index of antral pressure waves between t = 60 and 120 min (p = 0.032), but had no effect on esophago-gastric junction, pyloric, or duodenal pressures. CONCLUSIONS & INFERENCES: STW5-II has marked region-specific effects on gastric motility in humans, which may contribute to its therapeutic efficacy in functional dyspepsia.

Effects of Quinine on the Glycaemic Response to, and Gastric Emptying of, a Mixed-Nutrient Drink in Females and Males.

Intraduodenal quinine, in the dose of 600 mg, stimulates glucagon-like peptide-1 (GLP-1), cholecystokinin and insulin; slows gastric emptying (GE); and lowers post-meal glucose in men. Oral sensitivity to bitter substances may be greater in women than men. We, accordingly, evaluated the dose-related effects of quinine on GE, and the glycaemic responses to, a mixed-nutrient drink in females, and compared the effects of the higher dose with those in males. A total of 13 female and 13 male healthy volunteers received quinine-hydrochloride (600 mg ('QHCl-600') or 300 mg ('QHCl-300', females only) or control ('C'), intraduodenally (10 mL bolus) 30 min before a drink (500 kcal, 74 g carbohydrates). Plasma glucose, insulin, C-peptide, GLP-1, glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin were measured at baseline, for 30 min after quinine alone, and then for 2 h post-drink. GE was measured by 13C-acetate breath-test. QHCl-600 alone stimulated insulin, C-peptide and GLP-1 secretion compared to C. Post-drink, QHCl-600 reduced plasma glucose, stimulated C-peptide and GLP-1, and increased the C-peptide/glucose ratio and oral disposition index, while cholecystokinin and GIP were less, in females and males. QHCl-600 also slowed GE compared to C in males and compared to QHCl-300 in females (p < 0.05). QHCl-300 reduced post-meal glucose concentrations and increased the C-peptide/glucose ratio, compared to C (p < 0.05). Magnitudes of glucose lowering and increase in C-peptide/glucose ratio by QHCl-600 were greater in females than males (p < 0.05). We conclude that quinine modulates glucoregulatory functions, associated with glucose lowering in healthy males and females. However, glucose lowering appears to be greater in females than males, without apparent differential effects on GI functions.

Effects of intraduodenal or intragastric administration of a bitter hop extract (Humulus lupulus L.), on upper gut motility, gut hormone secretion and energy intake in healthy-weight men.

Gastrointestinal functions, particularly pyloric motility and the gut hormones, cholecystokinin and peptide YY, contribute to the regulation of acute energy intake. Bitter tastants modulate these functions, but may, in higher doses, induce GI symptoms. The aim of this study was to evaluate the effects of both dose and delivery location of a bitter hop extract (BHE) on antropyloroduodenal pressures, plasma cholecystokinin and peptide YY, appetite perceptions, gastrointestinal symptoms and energy intake in healthy-weight men. The study consisted of two consecutive parts, with part A including n = 15, and part B n = 11, healthy, lean men (BMI 22.6 ± 1.1 kg/m2, aged 25 ± 3 years). In randomised, double-blind fashion, participants received in part A, BHE in doses of either 100 mg ("ID-BHE-100") or 250 mg ("ID-BHE-250"), or vehicle (canola oil; "ID-control") intraduodenally, or in part B, 250 mg BHE ("IG-BHE-250") or vehicle ("IG-control") intragastrically. Antropyloroduodenal pressures, hormones, appetite and symptoms were measured for 180 min, energy intake from a standardised buffet-meal was quantified subsequently. ID-BHE-250, but not ID-BHE-100, had modest, and transient, effects to stimulate pyloric pressures during the first 90 min (P < 0.05), and peptide YY from t = 60 min (P < 0.05), but did not affect antral or duodenal pressures, cholecystokinin, appetite, gastrointestinal symptoms or energy intake. IG-BHE-250 had no detectable effects. In conclusion, BHE, when administered intraduodenally, in the selected higher dose, modestly affected some appetite-related gastrointestinal functions, but had no detectable effects when given in the lower dose or intragastrically. Thus, BHE, at none of the doses or routes of administration tested, has appetite- or energy intake-suppressant effects.

Association between Dietary Macronutrient Intake and Symptoms in Uninvestigated Dyspepsia: Evidence from a Population-Based, Cross-Sectional Study.

(1) Background: Limited evidence from laboratory-based studies suggests that specific dietary macronutrients, particularly fat, can induce dyspeptic symptoms. Through a population-based study, we investigated the relationship between dietary macronutrients and dyspeptic symptoms and sought to determine macronutrient intake thresholds to predict or prevent dyspepsia and reduce symptoms in patients with dyspepsia. (2) Methods: A total of 4763 Iranian people were enrolled in this population-based, cross-sectional study. Uninvestigated dyspepsia (UD) and its symptoms, including postprandial fullness, early satiation, and epigastric pain, were evaluated using a modified Persian version of the Rome III criteria. The dietary intakes of participants were evaluated using a validated food−frequency questionnaire. Receiver operating characteristic (ROC) curve analysis was used to calculate threshold intakes of dietary macronutrients to prevent UD in the general population. The analysis was then repeated in those with UD to calculate intake thresholds for reducing UD symptoms. (3) Results: Early satiation occurred in 6.3% (n = 302), postprandial fullness in 8.0% (n = 384) and epigastric pain in 7.8% (n = 371) of participants. The prevalence of UD was 15.2%. Compared with individuals without UD, those with UD had a lower intake of carbohydrates (48.2% vs. 49.1%) and a higher intake of fats (38.3% vs. 37.4%), while protein and energy intakes did not differ. Higher dietary fat and protein intakes were associated with a higher prevalence of postprandial fullness and epigastric pain, respectively. Macronutrient intakes to predict UD in the general population were <49% of energy from carbohydrates, >14.7% from protein, and >37.7% from fats. Carbohydrate, protein, and fat intakes to prevent symptoms among those with UD were calculated to be >48.2%, <14.6%, and <38.6%, respectively. (4) Conclusion: Higher carbohydrate intake and lower fat or protein intakes were associated with a lower likelihood of UD. Prospective studies carefully manipulating dietary macronutrient composition are warranted to investigate the value of dietary changes to improve symptoms in people with UD.

Quinine Effects on Gut and Pancreatic Hormones and Antropyloroduodenal Pressures in Humans-Role of Delivery Site and Sex.

CONTEXT: The bitter substance quinine modulates the release of a number of gut and gluco-regulatory hormones and upper gut motility. As the density of bitter receptors may be higher in the duodenum than the stomach, direct delivery to the duodenum may be more potent in stimulating these functions. The gastrointestinal responses to bitter compounds may also be modified by sex. BACKGROUND: We have characterized the effects of intragastric (IG) versus intraduodenal (ID) administration of quinine hydrochloride (QHCl) on gut and pancreatic hormones and antropyloroduodenal pressures in healthy men and women. METHODS: 14 men (26 ±â€…2 years, BMI: 22.2 ±â€…0.5 kg/m2) and 14 women (28 ±â€…2 years, BMI: 22.5 ±â€…0.5 kg/m2) received 600 mg QHCl on 2 separate occasions, IG or ID as a 10-mL bolus, in randomized, double-blind fashion. Plasma ghrelin, cholecystokinin, peptide YY, glucagon-like peptide-1 (GLP-1), insulin, glucagon, and glucose concentrations and antropyloroduodenal pressures were measured at baseline and for 120 minutes following QHCl. RESULTS: Suppression of ghrelin (P = 0.006), stimulation of cholecystokinin (P = 0.030), peptide YY (P = 0.017), GLP-1 (P = 0.034), insulin (P = 0.024), glucagon (P = 0.030), and pyloric pressures (P = 0.050), and lowering of glucose (P = 0.001) were greater after ID-QHCl than IG-QHCl. Insulin stimulation (P = 0.021) and glucose reduction (P = 0.001) were greater in females than males, while no sex-associated effects were found for cholecystokinin, peptide YY, GLP-1, glucagon, or pyloric pressures. CONCLUSION: ID quinine has greater effects on plasma gut and pancreatic hormones and pyloric pressures than IG quinine in healthy subjects, consistent with the concept that stimulation of small intestinal bitter receptors is critical to these responses. Both insulin stimulation and glucose lowering were sex-dependent.

Comparative Effects of the Branched-Chain Amino Acids, Leucine, Isoleucine and Valine, on Gastric Emptying, Plasma Glucose, C-Peptide and Glucagon in Healthy Men.

(1) Background: Whey protein lowers postprandial blood glucose in health and type 2 diabetes, by stimulating insulin and incretin hormone secretion and slowing gastric emptying. The branched-chain amino acids, leucine, isoleucine and valine, abundant in whey, may mediate the glucoregulatory effects of whey. We investigated the comparative effects of intragastric administration of leucine, isoleucine and valine on the plasma glucose, C-peptide and glucagon responses to and gastric emptying of a mixed-nutrient drink in healthy men. (2) Methods: 15 healthy men (27 ± 3 y) received, on four separate occasions, in double-blind, randomised fashion, either 10 g of leucine, 10 g of isoleucine, 10 g of valine or control, intragastrically, 30 min before a mixed-nutrient drink. Plasma glucose, C-peptide and glucagon concentrations were measured before, and for 2 h following, the drink. Gastric emptying of the drink was quantified using 13C-acetate breath-testing. (3) Results: Amino acids alone did not affect plasma glucose or C-peptide, while isoleucine and valine, but not leucine, stimulated glucagon (p < 0.05), compared with control. After the drink, isoleucine and leucine reduced peak plasma glucose compared with both control and valine (all p < 0.05). Neither amino acid affected early (t = 0-30 min) postprandial C-peptide or glucagon. While there was no effect on overall gastric emptying, plasma glucose at t = 30 min correlated with early gastric emptying (p < 0.05). (4) Conclusion: In healthy individuals, leucine and isoleucine lower postprandial blood glucose, at least in part by slowing gastric emptying, while valine does not appear to have an effect, possibly due to glucagon stimulation.

Effects of Bitter Substances on GI Function, Energy Intake and Glycaemia-Do Preclinical Findings Translate to Outcomes in Humans?

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.

Comparative Effects of Intragastric and Intraduodenal Administration of Quinine on the Plasma Glucose Response to a Mixed-Nutrient Drink in Healthy Men: Relations with Glucoregulatory Hormones and Gastric Emptying.

BACKGROUND: In preclinical studies, bitter compounds, including quinine, stimulate secretion of glucoregulatory hormones [e.g., glucagon-like peptide-1 (GLP-1)] and slow gastric emptying, both key determinants of postprandial glycemia. A greater density of bitter-taste receptors has been reported in the duodenum than the stomach. Thus, intraduodenal (ID) delivery may be more effective in stimulating GI functions to lower postprandial glucose. OBJECTIVE: We compared effects of intragastric (IG) and ID quinine [as quinine hydrochloride (QHCl)] administration on the plasma glucose response to a mixed-nutrient drink and relations with gastric emptying, plasma C-peptide (reflecting insulin secretion), and GLP-1. METHODS: Fourteen healthy men [mean ± SD age: 25 ± 3 y; BMI (in kg/m2): 22.5 ± 0.5] received, on 4 separate occasions, in double-blind, randomly assigned order, 600 mg QHCl or control, IG or ID, 60 min (IG conditions) or 30 min (IG conditions) before a mixed-nutrient drink. Plasma glucose (primary outcome) and hormones were measured before, and for 2 h following, the drink. Gastric emptying of the drink was measured using a 13C-acetate breath test. Data were analyzed using repeated-measures 2-way ANOVAs (factors: treatment and route of administration) to evaluate effects of QHCl alone and 3-way ANOVAs (factors: treatment, route-of-administration, and time) for responses to the drink. RESULTS: After QHCl alone, there were effects of treatment, but not route of administration, on C-peptide, GLP-1, and glucose (P < 0.05); QHCl stimulated C-peptide and GLP-1 and lowered glucose concentrations (IG control: 4.5 ± 0.1; IG-QHCl: 3.9 ± 0.1; ID-control: 4.6 ± 0.1; ID-QHCl: 4.2 ± 0.1 mmol/L) compared with control. Postdrink, there were treatment × time interactions for glucose, C-peptide, and gastric emptying, and a treatment effect for GLP-1 (all P < 0.05), but no route-of-administration effects. QHCl stimulated C-peptide and GLP-1, slowed gastric emptying, and reduced glucose (IG control: 7.2 ± 0.3; IG-QHCl: 6.2 ± 0.3; ID-control: 7.2 ± 0.3; ID-QHCl: 6.4 ± 0.4 mmol/L)  compared with control. CONCLUSIONS: In healthy men, IG and ID quinine administration similarly lowered plasma glucose, increased plasma insulin and GLP-1, and slowed gastric emptying. These findings have potential implications for lowering blood glucose in type 2 diabetes. This study was registered as a clinical trial with the Australian New Zealand Clinical Trials at www.anzctr.org.au as ACTRN12619001269123.

Serum irisin levels in metabolically healthy versus metabolically unhealthy obesity: A case-control study.

Background: Metabolically healthy obese (MHO) individuals appear to be protected or more resistant to the progression of obesity-related metabolic disorders. Hormonal regulation associated with adipose or muscular tissues such as irisin and leptin may facilitate the healthy metabolic profile of MHO cases. In this case-control study, the differences between serum level of irisin was investigated in metabolically unhealthy obese (MUO) and metabolically healthy obese (MHO) individuals. Methods: The study participants included obese individuals with metabolic syndrome (MetS) (n=51) and 2 control groups that included weight matched cases without MetS (n=51) and normal weight cases without MetS (n=51). Diagnosis of MetS was made based on the Adult Treatment Panel III (ATPIII) criteria. Serum levels of leptin and irisin were determined by enzyme-linked immune-sorbent assay (ELISA) kit. Receiver Operator Characteristic (ROC) curve, multiple linear regression, and one-way ANOVA analysis were used in SPSS 16 software. Significant level was set at 0.05. Results: Based on the statistical analysis, serum levels of irisin were 2.91±1.6, 3.14±1.4, and 4.47±3.23 (ng/mL) in MUO, MHO, and nonobese metabolically healthy participants, respectively (P = 0.001). Also, serum levels of leptin were 14.06±12.4, 11.2±9.3, and 7.09±7.1 (ng/mL) in MUO, MHO, and nonobese metabolically healthy cases, respectively (p=0.002). After adjusting for demographic variables, a significant association was found between irisin and study groups (ß = 0.77, P = 0.001), weight (ß=-0.03, p=0.014), BMI (ß=-0.11, p=0.006), TG (ß=-0.003, p=0.025), fat mass (ß=-0.04, p=0.046), and fat free mass (ß=0.08, p=0.014). Conclusion: Obese patients with/without MetS had lower level of irisin than normal weight participants.

Intragastric administration of the bitter tastant quinine lowers the glycemic response to a nutrient drink without slowing gastric emptying in healthy men.

The rate of gastric emptying and the release of gastrointestinal (GI) hormones are major determinants of postprandial blood-glucose concentrations and energy intake. Preclinical studies suggest that activation of GI bitter-taste receptors potently stimulates GI hormones, including glucagon-like peptide-1 (GLP-1), and thus may reduce postprandial glucose and energy intake. We evaluated the effects of intragastric quinine on the glycemic response to, and the gastric emptying of, a mixed-nutrient drink and the effects on subsequent energy intake in healthy men. The study consisted of 2 parts: part A included 15 lean men, and part B included 12 lean men (aged 26 ± 2 yr). In each part, participants received, on 3 separate occasions, in double-blind, randomized fashion, intragastric quinine (275 or 600 mg) or control, 30 min before a mixed-nutrient drink (part A) or before a buffet meal (part B). In part A, plasma glucose, insulin, glucagon, and GLP-1 concentrations were measured at baseline, after quinine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured. In part B, energy intake at the buffet meal was quantified. Quinine in 600 mg (Q600) and 275 mg (Q275) doses alone stimulated insulin modestly (P < 0.05). After the drink, Q600 and Q275 reduced plasma glucose and stimulated insulin (P < 0.05), Q275 stimulated GLP-1 (P < 0.05), and Q600 tended to stimulate GLP-1 (P = 0.066) and glucagon (P = 0.073) compared with control. Quinine did not affect gastric emptying of the drink or energy intake. In conclusion, in healthy men, intragastric quinine reduces postprandial blood glucose and stimulates insulin and GLP-1 but does not slow gastric emptying or reduce energy intake under our experimental conditions.

Comparing serum concentration of spexin among patients with metabolic syndrome, healthy overweight/obese, and normal-weight individuals.

Background: There are many factors related to etiology of metabolic syndrome (MetS) including obesity. Spexin, a peptide hormone released from adipose tissue, is the most down-regulated gene in obese, compared to non-obese adipose tissue. Hence, it potentially contributes to the progression and development of metabolic diseases. This study was designed to evaluate serum concentration of spexin in patients with MetS compared to weight-matched and normal-weight controls. Methods: In this case-control study, 153 participants (51 per group) were collected from October 2014 to June 2016. The study groups were all matched for age and sex and included overweight/obese individuals with MetS and 2 control groups without MetS (including weight-matched and normal-weight participants). Body composition and serum concentration of spexin and leptin were measured. Results: Serum leptin and spexin levels were significantly higher and lower, respectively, in normal-weight compared to overweight/obese groups with/without MetS (p< 0.02). No significant difference was observed in serum leptin and spexin concentrations between the overweight/obese groups with/without MetS (p≥ 0.05). Also, spexin, with cutoff value of 4.6, had 78% sensitivity and 82% specificity for diagnosing overweight/obese from normal-weight participants. Spexin had 78% sensitivity and specificity, with cutoff value of 4.35, in diagnosing MetS participants from normal-weight group. Conclusion: This study found no correlation between the circulating level of spexin and MetS development. Higher serum concentration of spexin in normal-weight adults compared to the obese participants illustrated the potential role of this novel peptide in obesity.

Adiponectin: An Indicator for Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS), a cluster of cardiometabolic risk factors, consider as a manifestation of obesity. However, a proportion of obese patients do not develop MetS. The aim of our study was to determine whether concentration of plasma adiponectin and leptin differ between metabolic unhealthy obese (MUO) patients and comparable age- and sex-matched control groups. METHODS: In this case-control study, we assigned 51 obese patients with MetS (MUO) in cases group and 102 metabolic healthy obese (MHO) and normal weight metabolic healthy subjects matched for age and gender to cases in control groups. The study was conducted between December 2014 and February 2016 in the Endocrinology Research Center of Tehran University of Medical Sciences, Tehran, Iran. We measured serum adiponectin, leptin, their ratio, and body composition in all subjects. RESULTS: No significant differences were observed between MHO and MUO in term of total fat mass and trunk fat (P>0.05). Compared to MHO and normal weight metabolic healthy subjects, MUO subjects had lower levels of plasma adiponectin (P<0.001) and lower plasma adiponectin to leptin ratio (P<0.001) and a higher level of plasma leptin (P<0.002). A Receiver Operator Characteristic curve was used to identify the ability of adiponectin and leptin level to predict the MetS. The area under the Receiver Operator Characteristic curve was 0.66 (P<0.01), 0.73 (P<0.001) and 0.75 (P<0.001) for leptin, adiponectin, and adiponectin/leptin ratio levels respectively. CONCLUSION: Our study introduced adiponectin and leptin as indicator of MetS and obesity respectively.

Effects of Intraduodenal Infusion of the Bitter Tastant, Quinine, on Antropyloroduodenal Motility, Plasma Cholecystokinin, and Energy Intake in Healthy Men.

BACKGROUND/AIMS: Nutrient-induced gut hormone release (eg, cholecystokinin [CCK]) and the modulation of gut motility (particularly pyloric stimulation) contribute to the regulation of acute energy intake. Non-caloric bitter compounds, including quinine, have recently been shown in cell-line and animal studies to stimulate the release of gastrointestinal hormones by activating bitter taste receptors expressed throughout the gastrointestinal tract, and thus, may potentially suppress energy intake without providing additional calories. This study aims to evaluate the effects of intraduodenally administered quinine on antropyloroduodenal pressures, plasma CCK and energy intake. METHODS: Fourteen healthy, lean men (25 ± 5 years; BMI: 22.5 ± 2.0 kg/m2) received on 4 separate occasions, in randomized, double-blind fashion, 60-minute intraduodenal infusions of quinine hydrochloride at doses totaling 37.5 mg ("Q37.5"), 75 mg ("Q75") or 225 mg ("Q225"), or control (all 300 mOsmol). Antropyloroduodenal pressures (high-resolution manometry), plasma CCK (radioimmunoassay), and appetite perceptions/gastrointestinal symptoms (visual analog questionnaires) were measured. Ad libitum energy intake (buffet-meal) was quantified immediately post-infusion. Oral quinine taste-thresholds were assessed on a separate occasion using 3-alternative forced-choice procedure. RESULTS: All participants detected quinine orally (detection-threshold: 0.19 ± 0.07 mmol/L). Intraduodenal quinine did not affect antral, pyloric or duodenal pressures, plasma CCK (pmol/L [peak]; control: 3.6 ± 0.4, Q37.5: 3.6 ± 0.4, Q75: 3.7 ± 0.3, Q225: 3.9 ± 0.4), appetite perceptions, gastrointestinal symptoms or energy intake (kcal; control: 1088 ± 90, Q37.5: 1057 ± 69, Q75: 1029 ±7 0, Q225: 1077 ± 88). CONCLUSIONS: Quinine, administered intraduodenally over 60 minutes, even at moderately high doses, but low infusion rates, does not modulate appetite-related gastrointestinal functions or energy intake.

Gastrointestinal Sensing of Meal-Related Signals in Humans, and Dysregulations in Eating-Related Disorders.

The upper gastrointestinal (GI) tract plays a critical role in sensing the arrival of a meal, including its volume as well as nutrient and non-nutrient contents. The presence of the meal in the stomach generates a mechanical distension signal, and, as gastric emptying progresses, nutrients increasingly interact with receptors on enteroendocrine cells, triggering the release of gut hormones, with lipid and protein being particularly potent. Collectively, these signals are transmitted to the brain to regulate appetite and energy intake, or in a feedback loop relayed back to the upper GI tract to further adjust GI functions, including gastric emptying. The research in this area to date has provided important insights into how sensing of intraluminal meal-related stimuli acutely regulates appetite and energy intake in humans. However, disturbances in the detection of these stimuli have been described in a number of eating-related disorders. This paper will review the GI sensing of meal-related stimuli and the relationship with appetite and energy intake, and examine changes in GI responses to luminal stimuli in obesity, functional dyspepsia and anorexia of ageing, as examples of eating-related disorders. A much better understanding of the mechanisms underlying these dysregulations is still required to assist in the development of effective management and treatment strategies in the future.

Intraduodenal Administration of L-Valine Has No Effect on Antropyloroduodenal Pressures, Plasma Cholecystokinin Concentrations or Energy Intake in Healthy, Lean Men.

Whey protein is rich in the branched-chain amino acids, L-leucine, L-isoleucine and L-valine. Thus, branched-chain amino acids may, at least in part, mediate the effects of whey to reduce energy intake and/or blood glucose. Notably, 10 g of either L-leucine or L-isoleucine, administered intragastrically before a mixed-nutrient drink, lowered postprandial blood glucose, and intraduodenal infusion of L-leucine (at a rate of 0.45 kcal/min, total: 9.9 g) lowered fasting blood glucose and reduced energy intake from a subsequent meal. Whether L-valine affects energy intake, and the gastrointestinal functions involved in the regulation of energy intake, as well as blood glucose, in humans, is currently unknown. We investigated the effects of intraduodenally administered L-valine on antropyloroduodenal pressures, plasma cholecystokinin, blood glucose and energy intake. Twelve healthy lean men (age: 29 ± 2 years, BMI: 22.5 ± 0.7 kg/m²) were studied on 3 separate occasions in randomised, double-blind order. Antropyloroduodenal pressures, plasma cholecystokinin, blood glucose, appetite perceptions and gastrointestinal symptoms were measured during 90-min intraduodenal infusions of L-valine at 0.15 kcal/min (total: 3.3 g) or 0.45 kcal/min (total: 9.9 g), or 0.9% saline (control). Energy intake from a buffet-meal immediately after the infusions was quantified. L-valine did not affect antral, pyloric (mean number; control: 14 ± 5; L-Val-0.15: 21 ± 9; L-Val-0.45: 11 ± 4), or duodenal pressures, plasma cholecystokinin (mean concentration, pmol/L; control: 3.1 ± 0.3; L-Val-0.15: 3.2 ± 0.3; L-Val-0.45: 3.0 ± 0.3), blood glucose, appetite perceptions, symptoms or energy intake (kcal; control: 1040 ± 73; L-Val-0.15: 1040 ± 81; L-Val-0.45: 1056 ± 100), at either load (p > 0.05 for all). In conclusion, intraduodenal infusion of L-valine, at loads that are moderately (3.3 g) or substantially (9.9 g) above World Health Organization valine requirement recommendations, does not appear to have energy intake- or blood glucose-lowering effects.

School-Based Nutrition Education Intervention Using Social Cognitive Theory for Overweight and Obese Iranian Adolescent Girls: A Cluster Randomized Controlled Trial.

Background Nowadays childhood obesity has become one the most challenging issue which is considered as a principle public health problem all around the world. This study was conducted with the aim of evaluating the impact of a 7-month school-based nutrition education intervention using social cognitive theory (SCT) to prevent obesity among overweight and obese adolescent girls. Method In this cluster randomized community trial after choosing schools, a total of 172 overweight and obese girl students participated in the study (87 in the intervention and 85 in the control group). A 7-month intervention based on SCT for students, their parents, and teachers was conducted. At baseline and end of the study, body mass index (BMI), waist circumstances (WCs), dietary intake, and psychological questionnaires regarding the SCT constructs were obtained. Results After 7 months, the mean of BMI and WCs reduced in the intervention group from 29.47 (4.05) to 28.5 (4.35) and from 89.65 (8.15) to 86.54 (9.76), respectively, but in comparison to the control group, they were not statistically significant ( p values .127 and .504, respectively). In the intervention group, nutritional behaviors and most of the psychological variables (self-efficacy, social support, intention, and situation) were improved in favor of the study and they were significant in comparison to the control group ( p < .05). Conclusion Although school-based nutrition education intervention using SCT did not change significantly BMI and WCs among the targeted population in this study, dietary habits as well as psychological factors improved significantly in the intervention group. This trial was registered in Iranian Registry of Clinical Trials, www.irct.ir (IRCT2013103115211N1).

Metabolic Syndrome Patients Have Lower Levels of Adropin When Compared With Healthy Overweight/Obese and Lean Subjects.

Metabolic syndrome (MetS), a cluster of cardiometabolic risk factors, is a challenging public health issue. The aim of current study was to test the hypothesis that concentrations of plasma adropin and leptin differ between patients with MetS and comparable age- and sex-matched control groups. This case-control study involved 153 subjects (51 per group). The study group included obese subjects with MetS and the two control groups included weight-matched subjects without MetS ("healthy": obese) and normal weight subjects without MetS. Body composition parameters were measured using bioelectrical impedance analysis. Plasma levels of adropin, leptin, and their ratio were measured. Leptin was significantly different between obese patients with/without MetS groups and normal weight subjects. Patients with MetS had higher levels of leptin (14 ± 12.4) compared with those without MetS (11.2 ± 9.3 vs. 7 ± 7.1 obese and normal weight without MetS, respectively; p = .002). Compared with healthy obese and normal weight subjects, MetS subjects had lower levels of plasma adropin ( p < .001) and a lower plasma adropin to leptin ratio ( p < .001), which remained significant when adjusted for body fat mass by analysis of covariance ( p < .001). This study demonstrates low levels of adropin are correlated with MetS and hence identify it as a potentially protective agent against MetS development. Variation in adropin levels may partly explain the "healthy obese" phenomenon.

Effects of coenzyme q10 supplementation on serum lipoproteins, plasma fibrinogen, and blood pressure in patients with hyperlipidemia and myocardial infarction.

BACKGROUND: Low plasma concentrations of coenzyme Q10 (CoQ10) have been associated with concentration of lipoproteins and other factors contributing to coronary heart diseases. OBJECTIVES: The present investigation aimed to improve the blood pressure and serum lipoproteins concentration in patients with myocardial infarction (MI) by CoQ10 supplementation. PATIENTS AND METHODS: In this randomized double-blinded controlled clinical trial, 52 Iranian patients with hyperlipidemia and MI were recruited to examine the effect of CoQ10 on serum total cholesterol (TC), LDL-C, HDL-C, triglyceride (TG), LDL-C/HDL-C ratio, TC/HDL-C ratio, fibrinogen, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Individuals were randomly allocated to two groups for receiving either 200 mg/d of CoQ10 or placebo for 12 weeks. RESULTS: There were not significant differences in serum LDL-C (2.70 ± 0.31 vs. 2.70 ± 0.35 mmol/L), TC (4.47 ± 0.33 vs. 4.93 ± 0.57 mmol/L), TG (2.48 ± 0.12 vs. 2.25 ± 0.69 mmol/L), and fibrinogen (2.08 ± 0.99 vs. 38.7 ± 0.64 mg/dL) between CoQ10 and placebo groups. After 12 weeks, a significant enhancement in serum HDL-C (1.44 ± 0.18 vs. 1.14 ± 0.18 mmol/L) level was observed between groups after the supplementation (P < 0.001). A significant reduction of TC, LDL-C, and fibrinogen and a significant increase in HDL-C concentration was observed in CoQ10 group after intervention (P < 0.001). Our assessment demonstrated statistically significant differences between the two groups in SBP and DBP after intervention (P < 0.001). ANCOVA also revealed significant differences in the ratio of LDL-C/HDL-C and TC/HDL-C between the two groups (1.89 ± 0.42 vs. 2.39 ± 0.38, P = 0.002; and 3.2 ± 0.5 vs. 4.24 ± 0.66, P = 0.01, respectively). A significant reduction of LDL-C/HDL-C and TC/HDL-C was observed in CoQ10 group (P < 0.001). CONCLUSIONS: Twelve-week supplementation with CoQ10 in patients with hyperlipidemia and MI can improve blood pressure, serum HDL-C as well as LDL-C/HDL-C and TC/HDL-C ratios; therefore, it might decrease the risk of frequent MI.