-
1.
Effects of intranasal oxytocin on satiety signaling in people with schizophrenia.
Warren, KR, Wehring, HJ, Liu, F, McMahon, RP, Chen, S, Chester, C, Kelly, DL
Physiology & behavior. 2018;:86-91
Abstract
Overweight and obesity in schizophrenia are prevalent, affecting half to three-quarters of people with schizophrenia. Hyperphagia and increased meal size have also been implicated as significant contributors to the weight gain problem. Oxytocin has shown to play a role in appetite control in humans and is considered an anorexigenic peptide. This two-day, within-subjects, challenge study involved the examination of satiety after administration of 24 IU oxytocin (intranasal) vs. placebo in participants with a DSM-IV diagnosis of schizophrenia (N = 16). Self reported satiety along with a preload-test meal paradigm were utilized as well as related laboratory measures (insulin, glucose, and leptin), and measures of taste and smell. There were no statistically significant differences between the groups on self-reported satiety or test meal consumption, insulin or glucose levels, or sensory measures. A significant treatment difference was found (F = 5.22, df = 1,97.6, p = 0.025), with a decrease in leptin in the oxytocin group post-administration, but no time effect (F = 1.67, df = 6,95.1, p = 0.180) or treatment by time interaction (F = 1.36. df = 3,4.16, p = 0.261). Despite the small sample and mostly negative findings, we encourage more work to use higher and repeated doses of oxytocin, and to further examine the effect of oxytocin on leptin in schizophrenia as this may be important for understanding both weight control and psychopathology.
-
2.
Acute Effect of Resistant Starch on Food Intake, Appetite and Satiety in Overweight/Obese Males.
Al-Mana, NM, Robertson, MD
Nutrients. 2018;(12)
Abstract
Several studies have linked increased intake of dietary fibre to improvement in the management of body weight. Dietary fibre from resistant starch (RS) has been shown to have an impact on food intake in normal weight individuals, but its role in obesity is unknown. The present study aimed to investigate the short-term effects of RS on appetite, satiety and postprandial metabolism in overweight/obese subjects. In this single-blind randomized crossover study, overweight/obese healthy males consumed a test breakfast and lunch containing either 48 g RS or a placebo. Postprandial qualitative appetite, glucose, insulin, and GLP-1 were measured every 30 min for 7 h. Energy intake values from an ad libitum dinner and for a 24-h period were assessed. Acute consumption of RS at breakfast/lunch significantly reduced the energy intake at the ad libitum dinner (p = 0.017). No significant effect over 24 h or qualitative feelings of satiety were observed. Significant treatment × time effects were found for postprandial glucose (p = 0.004) for RS compared to placebo, with a trend for higher C-peptide concentrations following RS. The postprandial insulin and GLP-1 responses were not significantly different. RS may indeed have short-term beneficial effects in obese individuals.
-
3.
Glucagon-Like Peptides 1 and 2 Are Involved in Satiety Modulation After Modified Biliopancreatic Diversion: Results of a Pilot Study.
Cazzo, E, Pareja, JC, Chaim, EA, Coy, CSR, Magro, DO
Obesity surgery. 2018;(2):506-512
Abstract
BACKGROUND This paper aimed to evaluate the influence of modified biliopancreatic diversion (BPD) on the levels of GLP-1 and GLP-2 and correlate them with satiety regulation. METHODS This is a pilot prospective cohort study that evaluated six mildly obese individuals with type 2 diabetes mellitus, which underwent modified BPD and were followed-up for 12 months. Levels of GLP-1 and GLP-2 after a standard meal tolerance test were determined and correlated with satiety scores obtained by means of a visual analogue scale (VAS). RESULTS There were significant changes in BMI (33 ± 2.2 versus 26.3 ± 2.2 kg/m2; p < 0.001), HbA1c (7.9 ± 1.6 versus 5.8 ± 1.2%; p = 0.026), total cholesterol (172.3 ± 11.1 versus 134.7 ± 16.1 mg/dL; p < 0.001), LDL-c (103.3 ± 13 versus 64.6 ± 12.2 mg/dL; p < 0.001), and postprandial GLP-2 (972.7 ± 326.2 versus 1993.2 ± 1024.7; p = 0. 044). None of the scores obtained in the VAS significantly changed after surgery. After surgery, there were significant correlations of VAS scores and GLP-1 levels in question 01 ("how hungry do you feel?"; R = -0.928; p = .008) and GLP-2 levels in questions 02 ("how full do you feel?" R = 0.943; p = 0.005) and 04 ("how much do you think you can eat now? R = -0.829; p = 0.042). CONCLUSIONS Modified BPD does not lead to significant changes in satiety evaluated by the VAS; different aspects of satiety regulation are correlated with the postprandial levels of GLP-1 (hunger feeling) and GLP-2 (satiation feeling and desire to eat) 1 year after modified BPD, signaling a specific postoperative gut hormone-related modulation of appetite.
-
4.
The Effect of an Encapsulated Nutrient Mixture on Food Intake and Satiety: A Double-Blind Randomized Cross-Over Proof of Concept Study.
Alleleyn, AME, van Avesaat, M, Ripken, D, Bleiel, SB, Keszthelyi, D, Wilms, E, Troost, FJ, Hendriks, HFJ, Masclee, AAM
Nutrients. 2018;(11)
Abstract
Activation of the intestinal brake by infusing nutrients into the distal small intestine with catheters inhibits food intake and enhances satiety. Encapsulation of macronutrients, which protects against digestion in the proximal gastrointestinal tract, can be a non-invasive alternative to activate this brake. In this study, we investigate the effect of oral ingestion of an encapsulated casein and sucrose mixture (active) targeting the distal small intestine versus a control product designed to be released in the stomach on food intake, satiety, and plasma glucose concentrations. Fifty-nine volunteers received the active and control product on two separate test days. Food intake was determined during an ad libitum meal 90 min after ingestion of the test product. Visual analogue scale scores for satiety and blood samples for glucose analysis were collected at regular intervals. Ingestion of the active product decreased food intake compared to the control product (655 kcal compared with 699 kcal, respectively, p < 0.05). The area under the curve (AUC) for hunger was decreased (p < 0.05) and AUC for satiety was increased (p < 0.01) after ingestion of the active product compared to the control product. Ingestion of an encapsulated protein-carbohydrate mixture resulted in inhibition of food intake compared to a non-encapsulated control product.
-
5.
The Neurocircuitry of fluid satiation.
Ryan, PJ
Physiological reports. 2018;(12):e13744
Abstract
Fluid satiation, or quenching of thirst, is a critical homeostatic signal to stop drinking; however, its underlying neurocircuitry is not well characterized. Cutting-edge genetically encoded tools and techniques are now enabling researchers to pinpoint discrete neuronal populations that control fluid satiation, revealing that hindbrain regions, such as the nucleus of the solitary tract, area postrema, and parabrachial nucleus, primarily inhibit fluid intake. By contrast, forebrain regions such as the lamina terminalis, primarily stimulate thirst and fluid intake. One intriguing aspect of fluid satiation is that thirst is quenched tens of minutes before water reaches the circulation, and the amount of water ingested is accurately calibrated to match physiological needs. This suggests that 'preabsorptive' inputs from the oropharyngeal regions, esophagus or upper gastrointestinal tract anticipate the amount of fluid required to restore fluid homeostasis, and provide rapid signals to terminate drinking once this amount has been consumed. It is likely that preabsorptive signals are carried via the vagal nerve to the hindbrain. In this review, we explore our current understanding of the fluid satiation neurocircuitry, its inputs and outputs, and its interconnections within the brain, with a focus on recent studies of the hindbrain, particularly the parabrachial nucleus.
-
6.
The amount and types of fatty acids acutely affect insulin, glycemic and gastrointestinal peptide responses but not satiety in metabolic syndrome subjects.
Chang, CY, Kanthimathi, MS, Tan, AT, Nesaretnam, K, Teng, KT
European journal of nutrition. 2018;(1):179-190
Abstract
PURPOSE Limited clinical evidence is available on the effects of amount and types of dietary fats on postprandial insulinemic and gastrointestinal peptide responses in metabolic syndrome subjects. We hypothesized that meals enriched with designated: (1) amount of fats (50 vs 20 g), (2) fats with differing fatty acid composition (saturated, SFA; monounsaturated, MUFA or n-6 polyunsaturated fatty acids, PUFA) would affect insulinemic and gastrointestinal peptide releases in metabolic syndrome subjects. METHODS Using a randomized, crossover and double-blinded design, 15 men and 15 women with metabolic syndrome consumed high-fat meals enriched with SFA, MUFA or n-6 PUFA, or a low-fat/high-sucrose (SUCR) meal. C-peptide, insulin, glucose, gastrointestinal peptides and satiety were measured up to 6 h. RESULTS As expected, SUCR meal induced higher C-peptide (45 %), insulin (45 %) and glucose (49 %) responses compared with high-fat meals regardless of types of fatty acids (P < 0.001). Interestingly, incremental area under the curve (AUC0-120min) for glucagon-like peptide-1 was higher after SUCR meal compared with MUFA (27 %) and n-6 PUFA meals (23 %) (P = 0.01). AUC0-120min for glucose-dependent insulinotropic polypeptide was higher after SFA meal compared with MUFA (23 %) and n-6 PUFA meals (20 %) (P = 0.004). Significant meal x time interaction (P = 0.007) was observed for ghrelin, but not cholecystokinin and satiety. CONCLUSIONS The amount of fat regardless of the types of fatty acids affects insulin and glycemic responses. Both the amount and types of fatty acids acutely affect the gastrointestinal peptide release in metabolic syndrome subjects, but not satiety.
-
7.
Just add water: Effects of added gastric distention by water on gastric emptying and satiety related brain activity.
Camps, G, Veit, R, Mars, M, de Graaf, C, Smeets, PA
Appetite. 2018;:195-202
Abstract
BACKGROUND Gastric distention contributes to meal termination. There is little research on the neural correlates of gastric distention by food. To date, neural measures have not been obtained concurrently with measurements of gastric distention. OBJECTIVES 1) To study how offering a small versus a large water load following a standardized nutrient load affects gastric distention over time. 2) To assess associations between satiety experiences and brain activity and the degree of gastric distention. METHOD 19 healthy males (age 22.2 ± 2.5 y, BMI 21.8 ± 1.5 kg/m2) participated in a randomized crossover study with two treatments: ingestion of a 500-kcal 150-mL liquid meal shake followed by a low (LV, 50 mL) or a high volume (HV, 350 mL) water load. At baseline and three times after ingestion satiety was scored, MRI scans were made to determine total gastric content volume (TGV) and functional MRI scans were made to measure cerebral blood flow (CBF). RESULTS TGV was significantly higher for HV compared to LV at all time points (p < 0.001) with relative differences between HV and LV of 292 ± 37 mL after ingestion, 182 ± 83 mL at t = 15 min and 62 ± 57 mL at t = 35 min. Hunger decreased (p = 0.023) and fullness increased (p = 0.030) significantly more for HV compared to LV. Ingestion increased CBF in the inferior frontal gyrus and the anterior insula, but there were no differences between treatments. There were no significant correlations between appetite ratings and CBF values. CONCLUSION Performing concurrent gastric MRI and CBF measurements can be used to investigate neural correlates of gastric distention. Increased distention did not induce significantly greater brain activation. Future research should further examine the role of the inferior frontal gyrus in satiety.
-
8.
Neural processing of food and monetary rewards is modulated by metabolic state.
Yousuf, M, Heldmann, M, Göttlich, M, Münte, TF, Doñamayor, N
Brain imaging and behavior. 2018;(5):1379-1392
Abstract
In humans, food is considered a powerful primary reinforcer, whereas money is a secondary reinforcer, as it gains a value through learning experience. Here, we aimed to identify the neural regions supporting the processing of food-related reinforcers, relate it to the neural underpinnings of monetary reinforcers, and explore their modulation by metabolic state (hunger vs satiety). Twenty healthy male participants were tested in two experimental sessions, once hungry and once satiated, using functional magnetic resonance imaging. Participants performed an associative learning task, receiving food or monetary rewards (in the form of images) on separate blocks. Irrespective of incentive type, both food and monetary rewards engaged ventral striatum, medial orbitofrontal cortex and amygdala, regions that have been previously associated with reward processing. Food incentives additionally engaged the opercular part of the inferior frontal gyrus and the insula, collectively known as a primary gustatory cortex. Moreover, in response to negative feedback (here, reward omission), robust activation was observed in anterior insula, supplementary motor area and lateral parts of the prefrontal cortex, including middle and inferior frontal gyrus. Furthermore, the interaction between metabolic state and incentive type resulted in supramarginal gyrus (SMG) activity, among other motor and sensory-related regions. Finally, functional connectivity analysis showed correlation in the hungry state between the SMG and mesolimbic regions, including the hippocampus, midbrain and cingulate areas. Also, the interaction between metabolic state and incentive type revealed coupling between SMG and ventral striatum. Whereas general purpose reward-related regions process incentives of different kinds, the current results suggest that the SMG might play a key role in integrating the information related to current metabolic state and available incentive type.
-
9.
GLP-1 and GLP-2 Levels are Correlated with Satiety Regulation After Roux-en-Y Gastric Bypass: Results of an Exploratory Prospective Study.
Cazzo, E, Pareja, JC, Chaim, EA, Geloneze, B, Barreto, MR, Magro, DO
Obesity surgery. 2017;(3):703-708
Abstract
BACKGROUND Changes in satiety regulation are known to play a pivotal role in the weight loss effects of Roux-en-Y gastric bypass (RYGB) and the mechanisms by which these changes occur are not entirely known. There are previous reports of the influence of GLP-1 to cause enhancement of satiation, but in regard to GLP-2, it remains unclear. This study aimed to determine whether there is a correlation between the levels of GLP-1 and GLP-2 and satiety regulation following RYGB. MATERIALS AND METHODS An exploratory prospective cohort study was made which enrolled 11 individuals who underwent RYGB and were followed-up for 12 months. GLP-1 and GLP-2 levels were determined before and after surgery and correlated with visual analogue scale scores for satiety. RESULTS GLP-2 AUC after standard meal tolerance test (MTT) was significantly higher following surgery (945.3 ± 449.1 versus 1787.9 ± 602.7; p = 0.0037). Postoperatively, GLP-1 AUC presented a significant negative correlation with the mean score obtained in the first question of the visual analogue scale ("how hungry do you feel?") (p = 0.008); GLP-2 AUC presented a significant positive correlation with the mean score of the third ("how full do you feel?") question, and a significant positive correlation with the mean score achieved in the fourth question ("how much do you think you can eat?"), (p = 0.005 and p = 0.042, respectively). CONCLUSION GLP-1 and GLP-2 were significantly correlated with satiety assessment within this sample. Further research is necessary to confirm these findings.
-
10.
Effects of liraglutide on weight, satiation, and gastric functions in obesity: a randomised, placebo-controlled pilot trial.
Halawi, H, Khemani, D, Eckert, D, O'Neill, J, Kadouh, H, Grothe, K, Clark, MM, Burton, DD, Vella, A, Acosta, A, et al
The lancet. Gastroenterology & hepatology. 2017;(12):890-899
Abstract
BACKGROUND Liraglutide, a long-acting GLP-1 receptor agonist, is approved for treatment of obesity; however, the mechanisms of action of liraglutide are incompletely understood. We compared effects of liraglutide versus placebo on gastric motor functions, satiation, satiety, and weight in obese individuals over 16 weeks. METHODS We did a randomised, double-blind, placebo-controlled pilot trial at a single centre (Mayo Clinic, Rochester, MN, USA). Participants were randomly allocated (1:1) by a computer generated randomisation schedule with no stratification to receive subcutaneous liraglutide (3·0 mg) or placebo, with standardised nutritional and behavioural counselling. Allocation was concealed from participants and study investigators. Otherwise healthy, local residents aged 18-65 years with body-mass index (BMI) 30 kg/m2 or higher were included. Liraglutide or placebo was escalated by 0·6 mg/day each week for 5 weeks and continued until week 16. The primary outcome was change in gastric emptying (delay relative to baseline) of solids T1/2 (time taken for half the radiolabelled meal to empty from the stomach), measured at 5 weeks and 16 weeks in all patients who received at least one dose of study drug, with missing data imputed. Secondary outcomes included weight loss at weeks 5 and 16, satiation (volume to fullness and maximum tolerated volume), satiety, and fasting and postprandial gastric volumes at 16 weeks. This trial is registered with ClinicalTrials.gov, number NCT02647944, and is closed to new participants. FINDINGS Between Dec 18, 2015, and Sept 1, 2016, 40 adults were enrolled and randomly allocated (19 to the liraglutide group; 21 to the placebo group). Compared with placebo, liraglutide delayed gastric emptying of solids at 5 weeks (median 70 min [IQR 32 to 151] vs 4 min [-21 to 18]; p<0·0001) and 16 weeks (30·5 min [-11 to 54] vs -1 min [-19 to 7]; p=0·025). There was also significantly greater weight loss in the liraglutide group than in the placebo group (at 5 weeks: median 3·7 kg [IQR 2·8 to 4·8] vs 0·6 kg [-0·3 to 1·4], p<0·0001; at 16 weeks: 5·3 kg [5·2 to 6·8] vs 2·5 kg [0·1 to 4·2], p=0·0009). Satiation, as assessed by maximum tolerated volume at 16 weeks, was lower in the liraglutide group (median 750 mL [IQR 651 to 908]) compared with the placebo group (1126 mL [944-1185]; p=0·054). No significant differences were noted between groups in terms of volume to fullness, satiety, or fasting and postprandial gastric volumes at week 16. Post-hoc analysis showed that the T1/2 of gastric emptying of solids at 5 weeks correlated with change in weight loss at week 16 with liraglutide (Rs 0·567, p=0·018). Nausea was the most common adverse event in the liraglutide group (12 of 19) compared with placebo (four of 21). INTERPRETATION Effects of liraglutide on weight loss are associated with delay in gastric emptying of solids; measurement of gastric emptying (eg, at 5 weeks of treatment) may be a biomarker of responsiveness and may help to select individuals for prolonged treatment with this class of drug. FUNDING US National Institutes of Health grant R56-DK67071.