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The effect of intestinal glucose load on neural regulation of food craving.
Stopyra, MA, Friederich, HC, Sailer, S, Pauen, S, Bendszus, M, Herzog, W, Simon, JJ
Nutritional neuroscience. 2021;(2):109-118
Abstract
Objectives: Excess sugar consumption, particularly in the form of sweetened beverages, has been identified as a pivotal contributor to the epidemic of obesity and associated metabolic disorders. However, the impact of sugar-sweetened beverages on food craving is still inconclusive. Therefore, the present study aimed to specifically investigate the effects of an intestinal glucose load on neural processing of food cues. Methods: Using a single-blind fMRI design, 26 normal-weight women were scanned on two occasions, after receiving either a glucose or water infusion directly into the stomach using a nasogastric tube, without being aware of the type of infusion. Participants had to either view neutral and food images, or were asked to distract themselves from these images by solving an arithmetic task. Results: In response to viewing high-caloric food cues, we observed increased activation in reward-related brain areas. During food distraction, fronto-parietal brain regions were recruited, which are commonly related to attentional deployment and hedonic valuation. Furthermore, activity in the dorsolateral prefrontal cortex showed increased functional connectivity with the insula and was correlated with subjective craving levels to food cues. Despite an increase of blood glucose levels in response to the glucose compared to the water infusion, neither subjective food craving nor neural regulation of food craving showed significant differences. Conclusions: These findings support a decreased satiation effect of sweet beverages, as intestinal glucose ingestion and signalling showed no significant effect on cortical brain circuits associated with food craving. This trial was registered at clinicaltrials.gov as NCT03075371.
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Magnetic Resonance Imaging Quantification of Fasted State Colonic Liquid Pockets in Healthy Humans.
Murray, K, Hoad, CL, Mudie, DM, Wright, J, Heissam, K, Abrehart, N, Pritchard, SE, Al Atwah, S, Gowland, PA, Garnett, MC, et al
Molecular pharmaceutics. 2017;(8):2629-2638
Abstract
The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targeted site for both locally and systemically acting drug products. Previous magnetic resonance imaging (MRI) studies offered novel insights on GIT liquid distribution in fasted humans in the stomach and small intestine, and showed that freely mobile liquid in the intestine collects in fairly distinct regions or "pockets". Based on this previous pilot data, we hypothesized that (1) it is possible to quantify the time course of the volume and number of liquid pockets in the undisturbed colon of fasted healthy humans following ingestion of 240 mL, using noninvasive MRI methods; (2) the amount of freely mobile water in the fasted human colon is of the order of only a few milliliters. Twelve healthy volunteers fasted overnight and underwent fasted abdominal MRI scans before drinking 240 mL (∼8 fluid ounces) of water. After ingesting the water they were scanned at frequent intervals for 2 h. The images were processed to quantify freely mobile water in the total and regional colon: ascending, transverse, and descending. The fasted colon contained (mean ± SEM) 11 ± 5 pockets of resting liquid with a total volume of 2 ± 1 mL (average). The colonic fluid peaked at 7 ± 4 mL 30 min after the water drink. This peak fluid was distributed in 17 ± 7 separate liquid pockets in the colon. The regional analysis showed that pockets of free fluid were found primarily in the ascending colon. The interindividual variability was very high; the subjects showed a range of number of colonic fluid pockets from 0 to 89 and total colonic freely mobile fluid volume from 0 to 49 mL. This is the first study measuring the time course of the number, regional location, and volume of pockets of freely mobile liquid in the undisturbed colon of fasted humans after ingestion of a glass of water. Novel insights into the colonic fluid environment will be particularly relevant to improve our understanding and design of the in vivo performance of controlled release formulations targeted to the colon. The in vivo quantitative information presented here can be input into physiologically based mechanistic models of dissolution and absorption, and can be used in the design and set up of novel in vitro performance tools predictive of the in vivo environment.
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Gastric Artery Embolization Trial for the Lessening of Appetite Nonsurgically (GET LEAN): Six-Month Preliminary Data.
Syed, MI, Morar, K, Shaikh, A, Craig, P, Khan, O, Patel, S, Khabiri, H
Journal of vascular and interventional radiology : JVIR. 2016;(10):1502-8
Abstract
PURPOSE To report 6-month safety and efficacy results of a pilot study of left gastric artery (LGA) embolization for the treatment of morbid obesity (ie, body mass index [BMI] > 40 kg/m(2)). MATERIALS AND METHODS Four white patients (three women; average age, 41 y [range, 30-54 y]; mean weight, 259.3 lbs [range, 199-296 lbs]; mean BMI, 42.4 kg/m(2) [range, 40.2-44.9 kg/m(2)]) underwent an LGA embolization procedure with 300-500-µm Bead Block particles via right common femoral or left radial artery approach. Follow-up included upper endoscopy at 3 days and 30 days if necessary and a gastric emptying study at 3 months. Tracked parameters included adverse events; weight change; ghrelin, leptin, and cholecystokinin levels; and quality of life (QOL; by Short Form 36 version 2 questionnaire). RESULTS Three minor complications (superficial gastric ulcerations healed by 30 d) occurred that did not require hospitalization. There were no serious adverse events. Average body weight change at 6 months was -20.3 lbs (n = 4; range, -6 to -38 lbs), or -8.5% (range, -2.2% to -19.1%). Average excess body weight loss at 6 months was -17.2% (range, -4.2% to -38.5%). Patient 4, who had diabetes, showed an improvement in hemoglobin A1c level (7.4% to 6.3%) at 6 months. QOL measures showed a general trend toward improvement, with the average physical component score improving by 9.5 points (range, 3.2-17.2) and mental component score improving by 9.6 points (range, 0.2-19.3) at 6 months. CONCLUSIONS Preliminary data support LGA embolization as a potentially safe procedure that warrants further investigation for weight loss in morbidly obese patients.
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abiliti Closed-Loop Gastric Electrical Stimulation System for Treatment of Obesity: Clinical Results with a 27-Month Follow-Up.
Horbach, T, Thalheimer, A, Seyfried, F, Eschenbacher, F, Schuhmann, P, Meyer, G
Obesity surgery. 2015;(10):1779-87
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Abstract
BACKGROUND The aim of the study was to evaluate the safety and effectiveness of a novel closed-loop gastric electric stimulation device (abiliti system) featuring a transgastric sensor to detect food intake and an accelerometer to record physical activity to induce and maintain lifestyle changes to treat obesity. METHODS In a prospective, multi-center study, 34 obese subjects (BMI of 42.1 ± 5.3 kg/m(2)) who passed an eligibility evaluation were implanted with the abiliti system. Safety evaluation included an endoscopic exam to assess the intragastric electrode healing. Efficacy evaluation at 1 year of therapy included weight loss, improvements in eating, and exercise behavior and quality of life. RESULTS The transgastric implant controlled by endoscopy was stable for all participants. At 12 months (12 M) the mean excess weight loss (EWL) was 28.7% (95%CI, 34.5 to 22.5%), and mean reduction in BMI was 4.8 ± 3.2 kg/m(2). At 27 months (27 M), the EWL was 27.5% (95% CI, 21.3% to 33.7%). Eating behavior, evaluated by the "Three Factor Eating Questionnaire", showed a significant increase in the cognition factor and decrease in the disinhibition and hunger factors at 12 M in comparison to baseline (p < 0.001). Participants significantly increased their weekly physical activity (p < 0.001). Quality of life was improved in 55.2% of the patients. CONCLUSIONS Gastric electrical stimulation with abiliti system in obese participants is well tolerated and leads to significant 12 M weight loss, which was stable to 27 M. We suggest that weight loss is achieved due to the assessed alteration of eating behavior in particular the reduction in disinhibition and hunger, and the measured increase in physical activity.
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Early experience with customized, meal-triggered gastric electrical stimulation in obese patients.
Miras, M, Serrano, M, Durán, C, Valiño, C, Canton, S
Obesity surgery. 2015;(1):174-9
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Abstract
BACKGROUND We report our initial gastric electrical stimulation experience using the abiliti® system for the treatment of obese patients followed for 1 year. METHOD Between March 2011 and June 2013, 27 obese patients (BMI 30 to 46 kg/m(2)) were enrolled in a prospective open label study and implanted with a gastric stimulator. The patients were provided with nutritional support, and sensor-based behavioral feedback. RESULTS At 12 months, percent excess weight loss (%EWL) obtained was 49.3 ± 19.2 % with no significant differences between gender or age sub-groups. The %EWL data were segmented into two groups according to BMI 30-40 kg/m(2) patients (obesity grade I and II) and BMI >40 kg/m(2), with the results of weight loss being significantly higher for the lower BMI group (59.1 ± 19.5 vs. 46.7 ± 13.4, respectively, p < 0.01). One subject requested to have his device explanted, and the minor postoperative adverse events were resolved without hospital admission. All patients experienced early satiety and reduced their intake. CONCLUSIONS After 12 months of follow-up, gastric electrical stimulation treatment appears to be a safe and effective option for weight loss in obese subjects. Long-term follow-up and further studies are warranted.
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Time-resolved MRI after ingestion of liquids reveals motility changes after laparoscopic sleeve gastrectomy--preliminary results.
Baumann, T, Kuesters, S, Grueneberger, J, Marjanovic, G, Zimmermann, L, Schaefer, AO, Hopt, UT, Langer, M, Karcz, WK
Obesity surgery. 2011;(1):95-101
Abstract
BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is generally considered a restrictive procedure. However, studies with nuclear medicine techniques have demonstrated that gastric motility changes occur following LSG. These motility changes could represent complementary mechanisms of weight loss. Therefore, we analyzed the stomach motility before and after LSG by means of dynamic MRI. METHODS In this prospective pilot study, five female patients with a mean BMI of 51.6 kg/m(2) underwent MRI 1 day before LSG and 6 days and 6 months after LSG. Dynamic steady-state free precession sequences were used to analyze the gastric motility after ingestion of 500 ml water with a temporal resolution of 0.86 s. Axial image stacks were also repeatedly acquired to determine the intragastric fluid volume over time. RESULTS Mean excess body mass index loss was 60.6% after 6 months. Dynamic analysis showed that antral propulsive peristalsis was preserved immediately after surgery and during follow-up, but fold speed increased significantly from 2.7 mm/s before LSG to 4.4 mm/s after 6 months. The sleeve itself remained without recognizable peristalsis in three patients and showed only uncoordinated or passive motion in two patients. Consequently, the fluid transport through the sleeve was markedly delayed, whereas the antrum showed accelerated propulsion with the emptying half-time decreasing from 16.5 min preoperatively to 7.9 min 6 months after surgery. CONCLUSIONS Owing to the LSG procedure, the stomach is functionally divided into a sleeve without propulsive peristalsis and an accelerated antrum. Accelerated emptying seems to be caused by faster peristaltic folds.
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Randomized phase II study of clinical effects of ghrelin after esophagectomy with gastric tube reconstruction.
Yamamoto, K, Takiguchi, S, Miyata, H, Adachi, S, Hiura, Y, Yamasaki, M, Nakajima, K, Fujiwara, Y, Mori, M, Kangawa, K, et al
Surgery. 2010;(1):31-8
Abstract
BACKGROUND Ghrelin is a peptide hormone with pleiotropic functions including stimulation of growth hormone secretion and appetite, and its levels decrease after esophagectomy. The aim of this study was to evaluate whether exogenous ghrelin administration can meliorate the postoperative decrease of oral food intake and body weight, which are serious complications after esophagectomy. METHODS This prospective randomized, placebo-controlled, clinical trial assigned a total of 20 patients with thoracic esophageal cancer who underwent radical operation into either a ghrelin (n =10) or placebo (n =10) group. Synthetic human ghrelin (3 microg/kg) or 0.9% saline placebo was administered intravenously twice daily for 10 days from the day after the start of food intake. The primary end point was calories of food intake. Comparison of appetite and changes in weight and body composition were also made between the 2 groups. RESULTS Intake of food calories was greater in ghrelin group than placebo group (mean 874 vs 605 kcal per day; P =.015). The appetite score tended to be greater in ghrelin group than placebo group (P =.094). Loss of weight was less in ghrelin group (-1% vs -3%; P =.019) and this attenuation was due largely to a decrease of lean body weight loss (0% vs -4%; P =.012). No side effects were observed in either groups. CONCLUSION These preliminary results suggest that administration of ghrelin after esophagectomy increased oral food intake and attenuated weight loss together with maintenance of lean body weight.
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Comparison of cardiac and gastric responses to vagal stimulation in hypertensive women.
Thor, PJ, Furgała, A, Mazur, M, Pośnik-Urbańska, A, Kolasińska-Kloch, W, Czarnecka, D, Kawecka-Jaszcz, K
Medical science monitor : international medical journal of experimental and clinical research. 2009;(10):CR504-511
Abstract
BACKGROUND The aim was to evaluate the interactions between the effects of vagal stimulation by sham feeding (nonbaroreflex) and deep breathing (baroreflex) on heart rate variability (HRV) and gastric myoelectrical activity (GMA) in pre- and postmenopausal women with essential hypertension. MATERIAL/METHODS One hundred five post- and premenopausal women with hypertension and 60 premenopausal normotensive women were observed. The study protocol consisted of 5 min of resting HRV followed by 5 min of deep breathing (DB), then 6 min of sham feeding (SF) with 30-min electrogastrography (EGG) before and after SF. The fasting plasma level of noradrenalin was measured. RESULTS The HRV parameter values at rest in the hypertensive group were half those in the control group (p<0.05). There were notably higher HRV parameter values in the premenopausal women. Plasma noradrenalin level was higher in the postmenopausal women (p=0.0009). The effect of DB was similar before and after menopause; however, HRV parameters in response to DB were lower in the hypertensive women than in the controls (p<0.05). In the controls there was a marked increase in the main HRV parameters in response to DB. In fasting electrogastrography the lowest normogastria percentage was observed in the postmenopausal women. EGG showed that only SF significantly affected the period dominant power (PDP) in all groups and the bradygastria percentage in the postmenopausal women. CONCLUSIONS This study suggests that the interactions that occur between the effects of non-baroreflex and baroreflex vagal stimulation in hypertensive women may contribute to gastric motility disorders and dyspeptic symptoms.
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The influence of the eradication of Helicobacter pylori on gastric ghrelin, appetite, and body mass index in patients with peptic ulcer disease.
Jang, EJ, Park, SW, Park, JS, Park, SJ, Hahm, KB, Paik, SY, Sin, MK, Lee, ES, Oh, SW, Park, CY, et al
Journal of gastroenterology and hepatology. 2008;:S278-85
Abstract
BACKGROUND AND AIM Helicobacter pylori (H. pylori) infection has been known to influence the gastric leptin and ghrelin secretion, for which the exact pathogenic role has not been documented yet. This study was designed to investigate the influence of H. pylori eradication on plasma or gastric levels of ghrelin, body mass index (BMI), and resultant levels of appetite in patients with peptic ulcer disease. METHODS Twenty-two patients with H. pylori-associated active duodenal or gastric ulcer were treated with 7 weeks of antisecretory medication followed with 7 days of eradication regimen. The plasma and tissue ghrelin levels, tumor necrosis factor-alpha (TNF-alpha) mRNA, BMI, and appetite scale were checked before and after treatment. An additional endoscopic examination was conducted in 10 patients taking both ulcer treatment and H. pylori eradication. RESULTS Gastric ghrelin mRNA expression was significantly increased after either ulcer healing or H. pylori eradication, whereas gastric TNF-alpha mRNA expression was decreased after ulcer treatment and H. pylori eradication. In parallel with these changes, the visual analog scales for hunger and prospective food consumption were significantly increased after ulcer healing and H. pylori eradication. An increase in BMI was not statistically related to ulcer healing and H. pylori eradication therapy. In the subgroup analysis of 10 patients performed with additional endoscopic examination, ulcer treatment was associated with increased plasma ghrelin level and tissue ghrelin expression irrelevant to H. pylori eradication. CONCLUSION Restored tissue levels of ghrelin and improved status of appetite was achieved with gastric ulcer healing and H. pylori eradication.
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Quality of life and symptomatic response to gastric neurostimulation for gastroparesis.
Velanovich, V
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2008;(10):1656-62; discussion 1662-3
Abstract
BACKGROUND Gastroparesis can be a difficult problem with patients suffering from nausea, vomiting, bloating, and pain intractable to medical management. Gastric neurostimulation has been developed as an adjunctive treatment for patients with diabetic and idiopathic gastroparesis unresponsive to pharmacologic and dietary treatment. The purpose of this study is to report symptomatic and quality-of-life response to gastric neurostimulation. METHODS This study was approved by the institutional review board, and patients had informed consent. The gastric neurostimulation device (Enterra therapy, Medtronic, Inc., Minneapolis, MN, USA) is approved by the Food and Drug Administration under the Humanitarian Device Exemption. Candidates for placement were patients with either idiopathic or diabetic gastroparesis who had symptomatic failure to dietary changes and to prokinetic and antiemetic drugs. Before placement, the patients' symptoms were recorded, and patients completed the Gastrointestinal Symptom Rating Scale (GSRS, three domains: dyspeptic syndrome, indigestion syndrome, and bowel dysfunction syndrome) and the Short Form-36 (SF-36, eight domains: physical functioning, role-physical, role-emotional, bodily pain, vitality, mental health, social functioning, general health, plus a health transition item). The device was surgically placed using a hybrid laparoscopic/open technique. Patients were followed and adjustments made on the device until satisfactory symptom control was achieved. At that time, patients completed both the GSRS and SF-36, and comparisons were made to preoperative values. RESULTS Forty-two patients had the device placed, 29 women, aged 41 (SD +14) years, 24 diabetic patients, 17 idiopathic patients, one postgastrectomy patient. Median follow-up was 12 months (range 1-42 months). There was a 2% immediate postoperative morbidity rate and 7% long-term morbidity rate (device extrusion). Thirty-one patients (74%) responded to gastric neurostimulation of variable degrees. Eleven patients had no response or had worsening symptoms. Of the patients who responded, there were statistically significant improvements in all three domains of the GSRS. Median scores (with interquartile ranges): dyspeptic syndrome, 9 (7-11.5) to 4 (2.5-6), p = 0.02; indigestion syndrome, 5 (2-7) to 4 (0-5), p = 0.05; bowel dysfunction syndrome, 3 (2-3) to 1 (0-1), p = 0.01. In the SF-36, there were statistically significant improvement in the health transition item, 4 (4-5) to 1.5 (1-3), p = 0.01; and social functioning domain, 25 (12.5-62.5) to 75 (50-87.5), p = 0.03. CONCLUSIONS Three quarters of gastroparesis patients responded to gastric neurostimulation to variable degrees. Gastrointestinal-specific symptoms are improved in responders. Patients felt that there health and social functioning (SF) improved, although there was no significant difference in the other domains. These results are encouraging considering that these patients had intractable symptoms with no other effective treatments available.