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Roux en Y gastric bypass increases ethanol intake in the rat.

ABSTRACT: Roux en Y gastric bypass (RYGB) surgery is currently the most effective therapy employed to treat obesity and its associated complications. In addition to weight loss and resolution of metabolic syndromes, such as diabetes, the RYGB procedure has been reported to increase alcohol consumption in humans. Using an outbred rodent model, we demonstrate that RYGB increases postsurgical ethanol consumption, that this effect cannot be explained solely by postsurgical weight loss and that it is independent of presurgical body weight or dietary composition. Altered ethanol metabolism and postsurgical shifts in release of ghrelin were also unable to account for changes in alcohol intake. Further investigation of the potential physiological factors underlying this behavioral effect identified altered patterns of gene expression in brain regions associated with reward following RYGB surgery. These findings have important clinical implications as they demonstrate that RYGB surgery leads directly to increased alcohol intake in otherwise alcohol nonpreferring rat and induces neurobiological changes in brain circuits that mediate a variety of appetitive behaviors.

SUBMITTER: Davis JF

PROVIDER: S-EPMC3970194 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Roux en Y gastric bypass increases ethanol intake in the rat.

Davis Jon F JF Tracy Andrea L AL Schurdak Jennifer D JD Magrisso Irwin J IJ Grayson Bernadette E BE Seeley Randy J RJ Benoit Stephen C SC

Obesity surgery 20130701 7

Roux en Y gastric bypass (RYGB) surgery is currently the most effective therapy employed to treat obesity and its associated complications. In addition to weight loss and resolution of metabolic syndromes, such as diabetes, the RYGB procedure has been reported to increase alcohol consumption in humans. Using an outbred rodent model, we demonstrate that RYGB increases postsurgical ethanol consumption, that this effect cannot be explained solely by postsurgical weight loss and that it is independe ...[more]

PMID: 23440511

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Project description:Abstract Objectives Our aim was to investigate in a real-life setting the use of machine learning for modelling the postprandial glucose concentrations in morbidly obese patients undergoing Roux-en-Y gastric bypass (RYGB) or one-anastomosis gastric bypass (OAGB). Methods As part of the prospective randomized open-label trial (RYSA), data from obese (BMI ≥35 kg/m2) non-diabetic adult participants were included. Glucose concentrations, measured with FreeStyle Libre, were recorded over 14 preoperative and 14 postoperative days. During these periods, 3-day food intake was self-reported. A machine learning model was applied to estimate glycaemic responses to the reported carbohydrate intakes before and after the bariatric surgeries. Results Altogether, 10 participants underwent RYGB and 7 participants OAGB surgeries. The glucose concentrations and carbohydrate intakes were reduced postoperatively in both groups. The relative time spent in hypoglycaemia increased regardless of the operation (RYGB, from 9.2 to 28.2%; OAGB, from 1.8 to 37.7%). Postoperatively, we observed an increase in the height of the fitted response curve and a reduction in its width, suggesting that the same amount of carbohydrates caused a larger increase in the postprandial glucose response and that the clearance of the meal-derived blood glucose was faster, with no clinically meaningful differences between the surgeries. Conclusions A detailed analysis of the glycaemic responses using food diaries has previously been difficult because of the noisy meal data. The utilized machine learning model resolved this by modelling the uncertainty in meal times. Such an approach is likely also applicable in other applications involving dietary data. A marked reduction in overall glycaemia, increase in postprandial glucose response, and rapid glucose clearance from the circulation immediately after surgery are evident after both RYGB and OAGB. Whether nondiabetic individuals would benefit from monitoring the post-surgery hypoglycaemias and the potential to prevent them by dietary means should be investigated. KEY MESSAGES The use of a novel machine learning model was applicable for combining patient-reported data and time-series data in this clinical study. Marked increase in postprandial glucose concentrations and rapid glucose clearance were observed after both Roux-en-Y gastric bypass and one-anastomosis gastric bypass surgeries. Whether nondiabetic individuals would benefit from monitoring the post-surgery hypoglycaemias and the potential to prevent them by dietary means should be investigated.

Project description:Bariatric surgery provides significant and durable improvements in glycemic control and hepatic steatosis, but the underlying mechanisms that drive improvements in these metabolic parameters remain to be fully elucidated. Recently, alterations in mitochondrial morphology have shown a direct link to nutrient adaptations in obesity. Here, we evaluate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics in a diet-induced obesity Sprague-Dawley (SD) rat model. Livers were harvested from adult male SD rats 90-days after either Sham or RYGB surgery and continuous high-fat feeding. We assessed expression of mitochondrial proteins involved in fusion, fission, mitochondrial autophagy (mitophagy) and biogenesis, as well as differences in citrate synthase activity and markers of oxidative stress. Gene expression for mitochondrial fusion genes, mitofusin 1 (Mfn1; P < 0.05), mitofusin 2 (Mfn2; P < 0.01), and optic atrophy 1 (OPA1; P < 0.05) increased following RYGB surgery. Biogenesis regulators, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α; P < 0.01) and nuclear respiratory factor 1 (Nrf1; P < 0.05), also increased in the RYGB group, as well as mitophagy marker, BCL-2 interacting protein 3 (Bnip3; P < 0.01). Protein expression for Mfn1 (P < 0.001), PGC1α (P < 0.05), BNIP3 (P < 0.0001), and mitochondrial complexes I-V (P < 0.01) was also increased by RYGB, and Mfn1 expression negatively correlated with body weight, insulin resistance, and fasting plasma insulin. In the RYGB group, citrate synthase activity was increased (P < 0.02) and reactive oxygen species (ROS) was decreased compared to the Sham control group (P < 0.05), although total antioxidant capacity was unchanged between groups. These data are the first to show an association between RYGB surgery and improved markers of liver mitochondrial dynamics. These observed improvements may be related to weight loss and reduced energetic demand on the liver, which could facilitate normalization of glucose homeostasis and protect against hepatic steatosis.

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Roux en Y gastric bypass increases ethanol intake in the rat.

Publications

Roux en Y gastric bypass increases ethanol intake in the rat.

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