Gastric Bypass-Related Effects on Glucose Control, β Cell Function and Morphology in the Obese Zucker Rat

Seyfried, Florian; Miras, Alexander D.; Rotzinger, Laura; Nordbeck, Arno; Corteville, Caroline; Li, Jia V.; Schlegel, Nicolas; Hankir, Mohammed K.; Fenske, Wiebke; Otto, Christoph; Jurowich, Christian

doi:10.1007/s11695-015-1882-5

Cited by 16 publications

(38 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In accordance with previous human (Kenler et al, 1990; Olbers et al, 2006; Thomas and Marcus, 2008) and rodent (Zheng et al, 2009; le Roux et al, 2011; Shin et al, 2011b; Hao et al, 2016) studies, we demonstrated that RYGB reduces HF intake and preference using an established rat model (Hankir et al, 2015; Seyfried et al, 2016). We found that this was associated with widespread reductions in brain MOR availability, particularly in the striatum.…”

Section: Discussionsupporting

confidence: 91%

“…All abdominal surgical procedures were performed after an overnight fast by a bariatric surgeon according to a previously established protocol (Hankir et al, 2015; Seyfried et al, 2016). Briefly, animals were anesthetized with 5% isoflurane in 2 l/min oxygen and then maintained on 1.8–2.3% isoflurane in 0.5 l/min oxygen.…”

Section: Methodsmentioning

confidence: 99%

“…Body weight and food intake were recorded daily for 12 weeks. This time-point after surgery corresponds to a stage of weight loss maintenance in our RYGB model (Hankir et al, 2015; Seyfried et al, 2016). …”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats

Hankir

Patt

et al. 2017

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

Brain μ-opioid receptors (MORs) stimulate high-fat (HF) feeding and have been implicated in the distinct long term outcomes on body weight of bariatric surgery and dieting. Whether alterations in fat appetite specifically following these disparate weight loss interventions relate to changes in brain MOR signaling is unknown. To address this issue, diet-induced obese male rats underwent either Roux-en-Y gastric bypass (RYGB) or sham surgeries. Postoperatively, animals were placed on a two-choice diet consisting of low-fat (LF) and HF food and sham-operated rats were further split into ad libitum fed (Sham-LF/HF) and body weight-matched (Sham-BWM) to RYGB groups. An additional set of sham-operated rats always only on a LF diet (Sham-LF) served as lean controls, making four experimental groups in total. Corresponding to a stage of weight loss maintenance for RYGB rats, two-bottle fat preference tests in conjunction with small-animal positron emission tomography (PET) imaging studies with the selective MOR radioligand [11C]carfentanil were performed. Brains were subsequently collected and MOR protein levels in the hypothalamus, striatum, prefrontal cortex and orbitofrontal cortex were analyzed by Western Blot. We found that only the RYGB group presented with intervention-specific changes: having markedly suppressed intake and preference for high concentration fat emulsions, a widespread reduction in [11C]carfentanil binding potential (reflecting MOR availability) in various brain regions, and a downregulation of striatal and prefrontal MOR protein levels compared to the remaining groups. These findings suggest that the suppressed fat appetite caused by RYGB surgery is due to reduced brain MOR signaling, which may contribute to sustained weight loss unlike the case for dieting.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats

Hankir

Patt

et al. 2017

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, research on the mechanism by which RYGB relieves diabetes‐associated obesity is important . The ZDF rat, a genetically engineered rat model of obesity associated with insulin resistance, dyslipidemia, and other complications, has been chosen to assess the effect of RYGB in many previous studies . In the present study, RYGB surgery obviously decreased endotoxemia‐associated indices, plasma LPS concentrations, and serum and adipose tissue concentrations of the inflammatory cytokines TNF‐α and IL‐1β.…”

Section: Discussionmentioning

confidence: 88%

“…Thus, we performed RYGB in Zucker diabetic fatty (ZDF) rats, a diabetic rat model of insulin resistance, dyslipidemia, and other complications. Many early and recent studies have used this experimental model to assess the effects of RYGB on glucose homeostasis . providing a quite precise approximation of obesity associated with T2D in humans.…”

Section: Introductionmentioning

confidence: 99%

Roux‐en‐Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats

Guo

Liu

et al. 2019

Journal of Diabetes

View full text Add to dashboard Cite

Background Postoperative modulation of the gut microbiome has been suggested to contribute to the metabolic benefits after metabolic surgery, but the mechanisms underlying these metabolic benefits remain unknown. Previously, we reported that Roux‐en‐Y gastric bypass (RYGB) surgery in Zucker diabetic fatty (ZDF) rats increased the abundance of Proteobacteria and Gammaproteobacteria. However, theoretically, these Gram‐negative bacteria may elevate lipopolysaccharide (LPS) levels. Therefore, in this study we further investigated the potential mechanisms by which RYGB improves glucose homeostasis, endotoxemia, and inflammatory stress in ZDF rats. Methods Rats were divided into three groups: (a) an RYGB group (RY); (b) a sham‐operated group pair‐fed with the RY group; and (c) a sham‐operated group fed ad libitum. Changes in LPS, cytokine levels, intestinal permeability (evaluated using the fluorescein isothiocyanate‐dextran method), and intestinal epithelial tight junction proteins zona occludins (ZO)‐1, occludin, and claudin‐1 were assessed 10 weeks postoperatively. Results Rats that underwent RYGB exhibited sustained weight loss and reduced glucose, as well as lower cytokine and LPS concentrations, than rats in the control groups. In the colonic epithelium, ZO1 and claudin‐1 (Cldn1) mRNA levels were higher in the RY than control groups. Intestinal permeability declined in the RY group and was positively correlated with LPS levels and negatively correlated with ZO‐1, occludin, and claudin‐1 expression. Conclusions The results demonstrate that RYGB can reduce the extent of endotoxemia and inflammation, which is associated with improved tight junction integrity and intestinal barrier strength. These effects may explain why a low level of inflammation is maintained after RYGB and the postoperative increase in Gram‐negative bacteria.

show abstract

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice

et al. 2020

View full text Add to dashboard Cite

Background Bariatric surgery is an effective treatment for type 2 diabetes. Early post-surgical enhancement of insulin secretion is key for diabetes remission. The full complement of mechanisms responsible for improved pancreatic beta cell functionality after bariatric surgery is still unclear. Our aim was to identify pathways, evident in the islet transcriptome, that characterize the adaptive response to bariatric surgery independently of body weight changes. Methods We performed entero-gastro-anastomosis (EGA) with pyloric ligature in leptin-deficient ob/ob mice as a surrogate of Roux-en-Y gastric bypass (RYGB) in humans. Multiple approaches such as determination of glucose tolerance, GLP-1 and insulin secretion, whole body insulin sensitivity, ex vivo glucose-stimulated insulin secretion (GSIS) and functional multicellular Ca 2+ -imaging, profiling of mRNA and of miRNA expression were utilized to identify significant biological processes involved in pancreatic islet recovery. Findings EGA resolved diabetes, increased pancreatic insulin content and GSIS despite a persistent increase in fat mass, systemic and intra-islet inflammation, and lipotoxicity. Surgery differentially regulated 193 genes in the islet, most of which were involved in the regulation of glucose metabolism, insulin secretion, calcium signaling or beta cell viability, and these were normalized alongside changes in glucose metabolism, intracellular Ca 2+ dynamics and the threshold for GSIS. Furthermore, 27 islet miRNAs were differentially regulated, four of them hubs in a miRNA-gene interaction network and four others part of a blood signature of diabetes resolution in ob/ob mice and in humans. Interpretation Taken together, our data highlight novel miRNA-gene interactions in the pancreatic islet during the resolution of diabetes after bariatric surgery that form part of a blood signature of diabetes reversal. Funding European Union's Horizon 2020 research and innovation programme via the Innovative Medicines Initiative 2 Joint Undertaking (RHAPSODY), INSERM, Société Francophone du Diabète, Institut Benjamin Delessert, Wellcome Trust Investigator Award (212625/Z/18/Z), MRC Programme grants (MR/R022259/1, MR/J0003042/1, MR/L020149/1), Diabetes UK (BDA/11/0004210, BDA/15/0005275, BDA 16/0005485) project grants, National Science Foundation (310030–188447), Fondation de l'Avenir.

show abstract

Gastric Bypass-Related Effects on Glucose Control, β Cell Function and Morphology in the Obese Zucker Rat

Abstract: Combined molecular, cellular and histological analyses of pancreatic function suggest that weight loss alone, and not the enhancement of GLP-1 responses, is predominant for the short-term β cell protective effects of RYGB.

Cited by 16 publications

References 37 publications

Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats

Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats

Roux‐en‐Y gastric bypass decreases endotoxemia and inflammatory stress in association with improvements in gut permeability in obese diabetic rats

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice

Contact Info

Product

Resources

About