scholarly journals A Pilot Study of Gut-Brain Signaling After Octreotide Therapy for Unintentional Weight Loss After Esophagectomy

2020 ◽  
Vol 106 (1) ◽  
pp. e204-e216
Author(s):  
Conor F Murphy ◽  
Nicholas Stratford ◽  
Neil G Docherty ◽  
Brendan Moran ◽  
Jessie A Elliott ◽  
...  

Abstract Background Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. Methods This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. Results Eight patients (7 male, age: mean ± SD 62.8 ± 9.4 years, postoperative BWL: 15.5 ± 5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ± 12.8 kg vs post: 69.2 ± 13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). Conclusion The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2128
Author(s):  
Marina Martín ◽  
Amaia Rodríguez ◽  
Javier Gómez-Ambrosi ◽  
Beatriz Ramírez ◽  
Sara Becerril ◽  
...  

Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (n = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks. A 25% restriction of HFD over 9 weeks leads to a 36% weight loss with regard to the group fed HFD ad libitum accompanied by normal values in adiposity index and food efficiency ratio (FER). This restriction also carried the normalization of NPY, AgRP and POMC hypothalamic mRNA expression, without changes in CART. Caloric restriction did not succeed in improving glucose homeostasis but reduced HFD-induced hyperinsulinemia. In conclusion, 25% restriction of HFD reduced adiposity and improved metabolism in experimental obesity, without changes in glycemia. Restriction of the HFD triggered the normalization of hypothalamic NPY, AgRP and POMC expression, as well as ghrelin and leptin levels.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Tohru Hira ◽  
Shono Ogasawara ◽  
Hiroshi Hara

AbstractIntroductionDietary calcium has been proposed to reduce appetite (or to enhance satiety) in human studies. However, underlying mechanisms are still unclear. In animal and cell studies, it has been demonstrated that activation of the calcium-sensing receptor induced secretion of anorexic gut hormones such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) from enteroendocrine cells. In the present study, we tested the hypothesis that calcium suppresses appetite thorough enhanced gut hormone secretion, by using rats.Materials and MethodsMale Sprague Dawley rats were maintained by feeding a standard diet (AIN-93G, n = 6–8 per group). As calcium sources, calcium chloride, calcium carbonate, and calcium lactate were tested. These calcium salts were orally preloaded in fasted rats by using a feeding tube, and subsequent food intake was monitored until 24 hours. To assess conditioned taste aversion, saccharin preference test was conducted after conditioning with calcium or lithium chloride. To investigate involvements of gut hormones such as CCK, GLP-1, and peptide-YY (PYY), specific receptor antagonists for respective gut hormones were intraperitoneally injected just after oral preload of calcium, and then food intake was monitored. Portal blood samples were collected 15 or 30 min after oral preload of calcium for measurement of gut hormones by ELISA.Results and discussionAt the same dose of calcium (150 mg/kg), preload of calcium chloride reduced food intake for 4 hours compared to preload of the control solution (P < 0.05), while other compounds had minor effects on food intake. Saccharin preference ratio was only reduced by conditioning with lithium chloride (P < 0.01), but not by that with calcium compounds, indicating no conditional taste aversion was occurred by calcium. Suppressive effect of calcium chloride on food intake was partially reversed by pretreatment with a PYY receptor antagonist (BIIE0246) but not by that with a CCK- or a GLP-1 receptor antagonist. Portal PYY concentrations were higher in calcium chloride-treated rats than in the control rats (P < 0.05), 15 min after the preload and re-feeding. Changes in serum calcium concentrations were not observed by preload of calcium.These results suggest that oral preload of calcium chloride reduces subsequent food intake via enhanced PYY secretion in rats.


Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2269 ◽  
Author(s):  
Lea Tischmann ◽  
Mathijs Drummen ◽  
Blandine Gatta-Cherifi ◽  
Anne Raben ◽  
Mikael Fogelholm ◽  
...  

Favorable effects of a high-protein/moderate-carbohydrate (HP/MCHO) diet after weight loss on body weight management have been shown. To extend these findings, associations between perception of hunger and satiety with endocannabinoids, and with glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) were assessed. At approximately 34 months after weight loss, 22 female and 16 male participants (mean age 64.5 ± 5.9 years; body mass index (BMI) 28.9 ± 3.9 kg/m2) completed a 48 h respiration chamber study. Participants were fed in energy balance with a HP/MCHO diet with 25%:45%:30% or a moderate-protein/high-carbohydrate (MP/HCHO) diet with 15%:55%:30% of energy from protein:carbohydrate:fat. Endocannabinoids and related compounds, relevant postprandial hormones (GLP-1, PYY), hunger, satiety, and ad libitum food intake were assessed. HP/MCHO versus MP/HCHO reduced hunger perception. The lower decremental area under the curve (dAUC) for hunger in the HP/MCHO diet (−56.6% compared to MP, p < 0.05) was associated with the higher AUC for 2-arachidonoylglycerol (2-AG) concentrations (p < 0.05). Hunger was inversely associated with PYY in the HP/MCHO group (r = −0.7, p < 0.01). Ad libitum food intake, homeostatic model assessment for insulin resistance (HOMA-IR) and incremental AUCs for gut peptides were not different between conditions. HP/MCHO versus MP/HCHO diet-induced reduction in hunger was present after 34 months weight maintenance in the post-obese state. HP/MCHO diet-induced decrease of hunger is suggested to interact with increased 2-AG and PYY concentrations.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Aldara Martin Alonso ◽  
Simon C Cork ◽  
Yue Ma ◽  
Myrtha Arnold ◽  
Herbert Herzog ◽  
...  

Abstract Background: Drugs that safely promote weight loss are required to treat the obesity crisis. The gut hormone peptide YY 3-36 (PYY3-36) is secreted post-prandially to suppress appetite via the Y2 receptor (Y2R). However, it is unclear whether PYY3-36 acts directly on the Y2R in the hypothalamic arcuate nucleus (ARC) or the afferent vagus nerve to inhibit food intake. Understanding the pathways by which PYY3-36 mediates its anorectic effects may facilitate the therapeutic targeting of this system. Methods: Y2R knockdown in the ARC (ARC-Y2R-KD) was achieved by stereotactic injection of Cre-expressing adeno-associated virus (AAV-Cre) in Y2R-flox C57Bl/6 mice. Y2R KD in the vagus was achieved by bilateral microinjection of AAV-Cre into the nodose ganglia (NG), where the cell bodies of vagal afferents reside. An alternative germline model of sensory nerve Y2R knockdown was generated using Nav1.8-Cre mice crossed with the Y2R-flox strain (Nav1.8-Y2R-KD). Feeding behaviour over 10 days in metabolic cages and the effects of endogenously released (after oral gavage of a nutrient bolus) or exogenously-administered PYY3-36 were investigated. Results: NG-Y2R-KD animals had 60% reduction in NG Y2R mRNA but remained responsive to cholecystokinin, a positive control of vagal functionality. This is the first example of receptor specific adult vagal deafferentation in mice. The Nav1.8-Y2R-KD model achieved 30% receptor KD. Feeding patterns in the ARC-Y2R-KD and NG-Y2R-KD groups were highly different from their controls, with smaller, faster meals in the KD groups. The anorectic effects (at the next meal) of endogenous PYY3-36 were attenuated in NG-Y2R-KD. Low dose exogenous PYY3-36 at 5 µg/kg significantly reduced 2h post injection food intake (FI) in the control groups (n=8; P=0.045) but this was abrogated in the NG-Y2R-KD group. This pattern was mirrored in the Nav1.8-Y2R-KD model: low dose PYY3-36 significantly reduced FI 1h post-IP compared to vehicle in controls (-0.19±0.05 g; P =0.036; n=8) but not in the Nav1.8-Y2R-KD (-0.004±0.111 g; n=3). Peripherally-administered PYY3-36 at a high dose (30 µg/kg) decreased FI in all groups, including ARC-Y2R-KD. Summary: These results suggest that endogenous PYY3-36 modulates meal patterning. The vagus nerve mediates physiological PYY3-36 signalling but alternative pathways, not exclusively via the ARC, may be more important in mediating its pharmacological effects. This is relevant for the design of more effective weight loss agents.


2019 ◽  
Vol 150 (3) ◽  
pp. 623-633 ◽  
Author(s):  
Kristine Beaulieu ◽  
Nuno Casanova ◽  
Pauline Oustric ◽  
Jake Turicchi ◽  
Catherine Gibbons ◽  
...  

ABSTRACT Background Continuous energy restriction (CER) is purported to be problematic because of reductions in fat-free mass (FFM), compensatory motivation to overeat, and weakened satiety. Intermittent energy restriction (IER) is an alternative behavioral weight loss (WL) strategy that may mitigate some of these limitations. Objective The objective of the DIVA study was to compare the effects of CER and IER on appetite when the degree of WL (≥5%) is matched. Methods Women with overweight/obesity (BMI 25.0–34.9 kg/m2; age 18–55 y) were recruited for this controlled-feeding RCT via CER (25% daily energy restriction) or IER (alternating ad libitum and 75% energy restriction days). Probe days were conducted at baseline and post-intervention to assess body composition, ad libitum energy intake and subjective appetite in response to a fixed-energy breakfast, and eating behavior traits. After baseline measurements, participants were allocated to CER (n = 22) or IER (n = 24). Per protocol analyses (≥5% WL within 12 wk) were conducted with use of repeated measures ANOVA. Results Thirty of 37 completers reached ≥5% WL [CER (n = 18): 6.3 ± 0.8% in 57 ± 16 d, IER (n = 12): 6.6 ± 1.1% in 67 ± 13 d; % WL P = 0.43 and days P = 0.10]. Fat mass [−3.9 (95% CI: −4.3, −3.4) kg] and FFM [−1.3 (95% CI: −1.6, −1.0) kg] were reduced post-WL (P &lt; 0.001), with no group differences. Self-selected meal size decreased post-WL in CER (P = 0.03) but not in IER (P = 0.19). Hunger AUC decreased post-WL (P &lt; 0.05), with no group differences. Satiety quotient remained unchanged and was similar in both groups. Both interventions improved dietary restraint, craving control, susceptibility to hunger, and binge eating (P &lt; 0.001). Conclusions Controlled ≥5% WL via CER or IER did not differentially affect changes in body composition, reductions in hunger, and improvements in eating behavior traits. This suggests that neither CER nor IER lead to compensatory adaptations in appetite in women with overweight/obesity. This trial was registered at clinicaltrials.gov as NCT03447600.


2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Yahia A. Kaabi ◽  
Mohiealdeen A. Khalifa

Cigarette smoking is commonly associated with weight loss and mechanisms for these weight changes are still elusive. Ghrelin is a peptide hormone that works in a neuroendocrine fashion to stimulate hunger and the desire for food intake. Ghrelin is also secreted in saliva, probably to enhance food taste. In the current study, we tested the direct impact of acute cigarette smoking on total ghrelin found in saliva.Methods. Blood and saliva samples were collected from 30 healthy nonsmoker male volunteers before and after one-cigarette smoke. Total ghrelin in serum and saliva was measured by ELISA based method.Results. Data showed a statistically significant reduction in salivary ghrelin after smoking(P<0.0001). In serum, total ghrelin levels were not affected before and after smoking(P=0.1362). Additionally, positive correlation was observed between serum and salivary ghrelin before smoking(r=0.4143andP=0.0158); however, this correlation was lost after smoking(r=0.1147andP=0.5461).Conclusion. Acute one-cigarette smoking can negatively affect ghrelin levels in saliva that might contribute to the dull food taste in smokers.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1694-1694
Author(s):  
Salima Taylor ◽  
Mandy Korpusik ◽  
Rachel Silver ◽  
Sai Krupa Das ◽  
Cheryl Gilhooly ◽  
...  

Abstract Objectives Self-monitoring daily dietary intake is recommended for weight loss and weight loss maintenance. However, current online platforms and applications are often burdensome, which may limit use. We conducted a pilot study to evaluate the accuracy of a new application designed to self-monitor dietary intake using natural spoken language (COCO; The Conversational Calorie Counter). Methods A total of 35 participants were enrolled in this pilot study. Participants were asked to record daily dietary intake using the COCO application for a period of at least five days. Two 24-hour dietary recalls were conducted during this time, between day three and day five, and served as the reference method for evaluating total energy intake (TEI; measured in kcal). Mean two-day energy intake was calculated for each assessment method for the days when the 24-hr recall and COCO data were collected. Self-reported TEI from COCO were compared to estimates obtained from the 24-hour dietary recalls by a paired samples t-test and a Pearson's correlation coefficient. Results On average, participants consumed three meals a day and recorded six days of food intake days with COCO (range: 4 to 10 days). The mean TEI was not significantly different between the two methods (1902 ± 621 kcal by 24-hour dietary recall and 1988 ± 1033 kcal by COCO, P = 0.59). There was a significant correlation between mean TEI measured with the two methods (r = 0.45; P = 0.006). In addition, a strong correlation was observed between the number of food items logged in COCO and those recalled in the 24-hour diet recalls (r = 0.82; P &gt;0.0001). Completion of the exit survey by 28 participants indicated that 43% would definitely or probably use the application again. Conclusions These results suggest that natural spoken language technology may have utility in applications to self-monitor food intake. Additional research is required to fully elucidate the validity of COCO in estimating dietary intake. Funding Sources This research was supported by the NIH Grant # 1R21HL118347–01 (SBR and JG), Quanta Computing, Inc., and the National Defense Science and Engineering Graduate fellowship.


Appetite ◽  
2014 ◽  
Vol 82 ◽  
pp. 78-84 ◽  
Author(s):  
Alexis L. Graham ◽  
Marci E. Gluck ◽  
Susanne B. Votruba ◽  
Jonathan Krakoff ◽  
Marie S. Thearle

1998 ◽  
Vol 274 (3) ◽  
pp. R610-R617 ◽  
Author(s):  
James E. Koch ◽  
Hong Ji ◽  
Mary D. Osbakken ◽  
Mark I. Friedman

Administration of the fructose analog 2,5-anhydro-d-mannitol (2,5-AM) elicits eating behavior in rats by its action in the liver. To evaluate whether the decrease in liver ATP levels produced by injection of 2,5-AM plays a role in the eating response, we examined the relationship between changes in eating behavior and liver adenine nucleotide levels over time in rats given 2,5-AM. Liver ATP concentrations decreased within 15 min after injection of 2,5-AM (300 mg/kg ip), remained low for up to 90 min postinjection, and returned to control (saline injection) levels by 4 h after treatment. Rats fed ad libitum initiated eating between 15 and 45 min after 2,5-AM treatment, after liver ATP levels had declined. Rats given food 1 h after 2,5-AM treatment increased food intake, but if access to food was delayed for 4 h after 2,5-AM injection the eating response was attenuated or absent. Whereas liver AMP and ADP levels were also altered by injection of 2,5-AM, changes in food intake did not consistently track changes in these nucleotides. The results support the hypothesis that the eating response to 2,5-AM is triggered by a decrease in liver ATP level.


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