Roux-en-Y gastric bypass in rats increases sucrose taste-related motivated behavior independent of pharmacological GLP-1-receptor modulation

Roux-en-Y gastric bypass (RYGB) surgery has been shown to decrease consummatory responsiveness of rats to high sucrose concentrations, and genetic deletion of glucagon-like peptide-1 receptors (GLP-1R) has been shown to decrease consummatory responsiveness of mice to low-sucrose concentrations. Here we assessed the effects of RYGB and pharmacological GLP-1R modulation on sucrose licking by chow-fed rats in a brief-access test that assessed consummatory and appetitive behaviors. Rats were tested while fasted presurgically and postsurgically and while nondeprived postsurgically and 5 h after intraperitoneal injections with the GLP-1R antagonist exendin-3(9–39) (30 μg/kg), agonist exendin-4 (1 μg/kg), and vehicle in 30-min sessions during which a sucrose concentration series (0.01–1.0 M) was presented in 10-s trials. Other rats were tested postsurgically or 15 min after peptide or vehicle injection while fasted and while nondeprived. Independent of food-deprivation state, sucrose experience, or GLP-1R modulation, RYGB rats took 1.5–3× as many trials as sham-operated rats, indicating increased appetitive behavior. Under nondeprived conditions, RYGB rats with presurgical sucrose experience licked more to sucrose relative to water compared with sham-operated rats. Exendin-4 and exendin-3(9–39) impacted 0.3 M sucrose intake in a one-bottle test, but never interacted with surgical group to affect brief-access responding. Unlike prior reports in both clearly obese and relatively leaner rats given RYGB and in GLP-1R knockout mice, we found that neither RYGB nor GLP-1R blockade decreased consummatory responsiveness to sucrose in our less obese chow-fed rats. Collectively, these results highlight the fact that changes in taste-driven motivated behavior to sucrose after RYGB and/or GLP-1R modulation are very model and measure dependent.

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Gastric bypass reduces fat intake and preference

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00139.2011 ◽

2011 ◽

Vol 301 (4) ◽

pp. R1057-R1066 ◽

Cited By ~ 151

Author(s):

Carel W. le Roux ◽

Marco Bueter ◽

Nadine Theis ◽

Malin Werling ◽

Hutan Ashrafian ◽

...

Keyword(s):

Gastric Bypass ◽

Taste Aversion ◽

Conditioned Taste Aversion ◽

Corn Oil ◽

Caloric Intake ◽

Consummatory Behavior ◽

High Fat ◽

Glucagon Like Peptide 1 ◽

Total Fat ◽

Access Test

Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty ( P = 0.046). Gastric bypass reduced total fat and caloric intake ( P < 0.001) and increased standard low-fat chow consumption compared with sham controls ( P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests ( P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups ( P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation.

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Differential Gurmarin Suppression of Sweet Taste Responses in Rat Solitary Nucleus Neurons

Journal of Neurophysiology ◽

10.1152/jn.00215.2003 ◽

2003 ◽

Vol 90 (2) ◽

pp. 911-923 ◽

Cited By ~ 12

Author(s):

Christian H. Lemon ◽

Toshiaki Imoto ◽

David V. Smith

Keyword(s):

Cluster Analysis ◽

Sucrose Concentration ◽

Hierarchical Cluster ◽

Initial Response ◽

Sweet Taste ◽

Induced Response ◽

Response Suppression ◽

Response Profiles ◽

Neuronal Type ◽

Concentration Series

We examined the effect of the sweet transduction blocker gurmarin on taste responses recorded from neurons in the rat solitary nucleus (NST) to determine how gurmarin sensitivity is distributed across neuronal type. Initially, responses evoked by washing the anterior tongue and palate with 0.5 M sucrose, 0.1 M NaCl, 0.01 M HCl, and 0.01 M quinine-HCl were recorded from 35 neurons. For some cells, responses to a sucrose concentration series (0.01–1.0 M) or an array of sweet-tasting compounds were also measured. Gurmarin (10 μg/ml, 2–4 ml) was then applied to the tongue and palate. Stimuli were reapplied after 10–15 min. Neurons were segregated into groups based on similarities among their initial response profiles using hierarchical cluster analysis (HCA). Results indicated that sucrose responses recorded from neurons representative of each HCA-defined class were suppressed by gurmarin. However, a disproportionate percentage of cells in each group displayed sucrose responses that were substantially attenuated after gurmarin treatment. Postgurmarin sucrose responses recorded from neurons that composed 57% of class S, 40% of class N, and 33% of class H were suppressed by ≥50% relative to control. On average, attenuation was statistically significant only in class S and N neurons. Although the magnitude of gurmarin-induced response suppression did not differ across sucrose concentration, responses to different sweet-tasting compounds were differentially affected. Responses to NaCl, HCl, or quinine were not suppressed by gurmarin. Results suggest that information from gurmarin-sensitive and -insensitive receptor processes converges onto single NST neurons.

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Roux-en-Y gastric bypass increases glycaemic variability and time in hypoglycaemia in patients with obesity and pre-diabetes/type 2 diabetes mellitus: a prospective cohort study

10.2337/figshare.13260275.v1 ◽

2020 ◽

Author(s):

Ibiyemi Ilesanmi ◽

George Tharakan ◽

Kleopatra Alexiadou ◽

Preeshila Behary ◽

Haya Alessimii ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gastric Bypass ◽

Diabetes Type 2 ◽

Diabetes Type ◽

Glucose Measurement ◽

Glycaemic Variability ◽

Study Objective ◽

Post Surgery ◽

Glucagon Like Peptide 1

Objective: Roux-en-Y gastric bypass (RYGB) is an established treatment for type 2 diabetes. The study objective was to establish RYGB’s effects on glycaemic variability (GV) and hypoglycaemia. Research Design and Methods: Prospective observational study of 10 participants with pre-diabetes/Type 2 diabetes undergoing RYGB, studied before surgery (Pre), 1 month (1m), 1 year (1y) and 2 years (2y) post-surgery with continuous glucose measurement (CGM). A mixed meal test (MMT) was performed at Pre, 1m and 1y. [ClinicalTrials.gov NCT01945840] Results: After RYGB, mean CGM glucose fell (at 1m, 1y and 2y), and GV increased (at 1y and 2y). Fifty percent (5/10) of participants exhibited a percentage time in range <3.0 mmol/L [54 mg/dl] (%TIR<3.0) greater than the consensus target of 1% at 1y or 2y. Peak glucagon-like peptide-1 (GLP-1) and glucagon area-under-curve (AUC) during MMT were respectively positively and negatively associated with contemporaneous %TIR<3.0. Conclusions: Patients undergoing RYGB are at risk of developing post-bariatric hypoglycaemia due to a combination of reduced mean glucose, increased GV and increased GLP-1 response.

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Brunner’s Gland Hyperplasia in a Patient after Roux-Y Gastric Bypass: An Important Pitfall in GLP-1 Receptor Imaging

Case Reports in Endocrinology ◽

10.1155/2020/4510910 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Matthias Hepprich ◽

Kwadwo Antwi ◽

Beatrice Waser ◽

Jean Claude Reubi ◽

Damian Wild ◽

...

Keyword(s):

Bariatric Surgery ◽

Gastric Bypass ◽

Receptor Imaging ◽

Brunner's Glands ◽

Pet Ct ◽

Brunner’S Glands ◽

Diagnostic Role ◽

Glucagon Like Peptide 1 ◽

Tracer Accumulation

Severe cases of postprandial hypoglycaemia after bariatric surgery can be a diagnostic and therapeutic challenge. The diagnostic role of 68Ga-DOTA-Exendin-4 PET/CT in postbariatric hypoglycaemia for further treatment decisions is unclear. We present a case of a 50-year-old woman with frequent and severe postprandial hypoglycaemic (≤2.5 mmol/L) episodes starting three years after Roux-Y gastric bypass. Despite strict dietary adherence and several medical therapies, the patient remained severely affected, and 68Ga-DOTA-Exendin-4 PET/CT was performed to exclude atypical presentation of an insulinoma or nesidioblastosis. No pancreatic abnormalities were found, but intensive tracer accumulation in the first and second part of the duodenum was detected, which proved to be hyperplastic Brunner’s glands on histology and were strongly positive for the glucagon-like peptide-1 receptor. This case provides histopathological verification that duodenal 68Ga-DOTA-Exendin-4 uptake is caused by uptake in Brunner’s glands and points to a potential relationship between bariatric surgery and Brunner’s glands.

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Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery

International Journal of Obesity ◽

10.1038/ijo.2016.121 ◽

2016 ◽

Vol 40 (11) ◽

pp. 1699-1706 ◽

Cited By ~ 83

Author(s):

M S Svane ◽

N B Jørgensen ◽

K N Bojsen-Møller ◽

C Dirksen ◽

S Nielsen ◽

...

Keyword(s):

Gastric Bypass ◽

Food Intake ◽

Bypass Surgery ◽

Peptide Yy ◽

Gastric Bypass Surgery ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Mechanisms of action of a carbohydrate-reduced, high-protein diet in reducing the risk of postprandial hypoglycemia after Roux-en-Y gastric bypass surgery

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy310 ◽

2019 ◽

Vol 110 (2) ◽

pp. 296-304 ◽

Cited By ~ 3

Author(s):

Daniel Kandel ◽

Kirstine Nyvold Bojsen-Møller ◽

Maria Saur Svane ◽

Amirsalar Samkani ◽

Arne Astrup ◽

...

Keyword(s):

Gastric Bypass ◽

Insulin Secretion ◽

Cell Function ◽

Gastric Bypass Surgery ◽

High Protein Diet ◽

Glucagon Secretion ◽

Glucose Variability ◽

High Protein ◽

Β Cell Function ◽

Glucagon Like Peptide 1

ABSTRACT Background Postprandial hypoglycemia is a risk after Roux-en-Y gastric bypass (RYGB). Objectives We speculated that a carbohydrate-reduced, high-protein (CRHP) diet might reduce the risk of hypoglycemia and therefore compared the acute effects of a conventionally recommended (CR) diet and CRHP diet [55/30 energy percent (E%) carbohydrate and 15/30 E% protein, respectively] in RYGB patients. Methods Ten individuals (2 males, 8 females, mean ± SD age 47 ± 7 y; stable body mass index 31 ± 6 kg/m2; 6 ± 3 y post-RYGB) with recurrent postprandial hypoglycemia documented by plasma glucose (PG) ≤3.4 mmol/L were examined on 2 d with isoenergetic CRHP or CR diets comprising a breakfast and subsequent lunch meal. Results Peak PG was significantly reduced on the CRHP diet after breakfast and lunch by 11% and 31% compared with the CR diet. Nadir PG increased significantly on CRHP (by 13% and 9%). Insulin secretion was reduced, and glucagon secretion increased on the CRHP diet after both meals. Glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide secretion were lower after lunch but unaltered after breakfast on CRHP; β-cell function and insulin clearance were unchanged. Conclusions The CRHP diet lowered glucose excursions and reduced insulin secretion and incretin hormone responses, but enhanced glucagon responses compared with the CR diet. Taken together, the results may explain the decreased glucose variability and lower risk of postprandial hypoglycemia. This study was registered at clinicaltrials.gov as NCT02665715.

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