Mechanisms underlying weight loss and metabolic improvements in rodent models of bariatric surgery

Arble, Deanna M.; Sandoval, Darleen A.; Seeley, Randy J.

doi:10.1007/s00125-014-3433-3

Cited by 56 publications

(57 citation statements)

References 116 publications

(162 reference statements)

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“…Similarly, there were no significant changes in cumulative food intake in either genotype. Previous research indicates that an initial reduction in caloric intake is key for the weight loss observed from bariatric surgery in rodents (4,26,27) . However, in this study, we do not observe these early changes in food intake within the WT or Magel2 mouse.…”

Section: Discussionmentioning

confidence: 99%

Sleeve gastrectomy leads to weight loss in the Magel2 knockout mouse

Arble

Pressler

Sorrell

et al. 2016

Surgery for Obesity and Related Diseases

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Background Prader-Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia, obesity, cardiopulmonary diseases, and increased mortality. While successful weight loss improves health in PWS, few treatments cause sustained weight loss in obese patients let alone obese individuals with PWS. Objectives The present study uses the Magel2 knockout (KO) mouse, an animal model of PWS, to conduct a preclinical study on the efficacy of Sleeve Gastrectomy (SG) in PWS. Setting Academic Research Laboratory, United States. Methods We performed sham or SG surgeries in 24-28 week old male Magel2 KO and wild-type littermate control mice (WT) who had been maintained on a high-fat diet for 10 weeks. We monitored body weight, food intake, and fat and lean mass pre- and post-operatively. Fasting glucose, glucose tolerance, and counterregulation were measured post-operatively. Results Magel2 KO animals had similar recovery and mortality rates compared to WT. SG resulted in similar weight loss, by specifically loss of fat but not lean mass, in both Magel2 KO and WT mice. SG also resulted in significantly lower fasting glucose levels and a reduction in fat intake in both Magel2 KO and WT mice. We also found that Magel2 KO mice failed to increase their food intake in response to the glucoprivic agent, 2-deoxy-D-glucose (2DG) suggesting impaired glucose counterregulation, but this occurred regardless of surgical status. All results were considered significant when P < 0.05. Conclusions We find in this mouse model of PWS, SG is a safe, effective strategy for weight and fat loss.

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Section: Discussionmentioning

confidence: 99%

Sleeve gastrectomy leads to weight loss in the Magel2 knockout mouse

Arble

Pressler

Sorrell

et al. 2016

Surgery for Obesity and Related Diseases

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“…While many have hypothesized “mechanical” explanations for these effects (i.e. meal-size restriction and/or malabsorption), such mechanisms do not account for the broad effects on physiology seen after surgery [2], [3]. In support of this, the metabolic effects of the two most commonly used operations, Roux-en Y gastric bypass and vertical sleeve gastrectomy (VSG), result in surprisingly similar physiologic and behavioral effects despite the gross anatomic differences.…”

Section: Introductionmentioning

confidence: 99%

Weight loss independent changes in adipose tissue macrophage and T cell populations after sleeve gastrectomy in mice

Frikke-Schmidt

Zamarron

O’Rourke

et al. 2017

Molecular Metabolism

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ObjectiveIn addition to adipocytes, adipose tissue contains large numbers of immune cells. A wide range of evidence links the activity of these cells to regulation of adipocyte and systemic metabolic function. Bariatric surgery improves several aspects of metabolic derangements and at least some of these effects occur in a weight-loss independent manner. We sought to investigate the impact of vertical sleeve gastrectomy (VSG) on adipose immune cell frequencies.MethodsWe analyzed the frequencies of immune cells within distinct adipose tissue depots in obese mice that had VSG or sham surgery with a portion of the latter group pair-fed such that their body mass was matched to the VSG animals.ResultsWe demonstrate that VSG induced a shift in the epididymal adipose tissue leukocyte profile including increased frequencies of CD11c− macrophages, increased frequencies of T cells (CD4+, CD8+, and CD4−/CD8− T cells all increased), but a significantly decreased frequency of adipose tissue dendritic cells (ATDC) that, despite the continued high fat feeding of the VSG group, dropped below control diet levels.ConclusionsThese results indicate that VSG induces substantial changes in the immune populations residing in the adipose depots independent of weight loss.

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“…4 Traditionally, the effects of bariatric surgery have been attributed to the mechanical aspects of these procedures, such as restriction, malabsorption, and changes in gut hormones that contribute to improvements in glucose regulation and satiety as well as reduced food intake. 11 Current evidence from clinical and experimental models of these procedures suggests that metabolic programming resulting from gastrointestinal tract manipulation may be key to weight loss and improvement of other metabolic complications. Among the many potential mediators, bile acid signaling seems to play an important role in modulating the beneficial effects of bariatric surgery.…”

Section: Does Bariatric Surgery Provide a Solution To The Current mentioning

confidence: 99%

Bile acid signaling and bariatric surgery

et al. 2017

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The rapid worldwide rise in obesity rates over the past few decades imposes an urgent need to develop effective strategies for treating obesity and associated metabolic complications. Bariatric surgical procedures, such as Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), currently provide the most effective treatment for obesity and type 2 diabetes (T2D), as well as for non-alcoholic steatohepatitis (NASH). However, the underlying mechanisms of the beneficial effects of bariatric surgery remain elusive. Recent studies have identified bile acids as potential signaling molecules involved in the beneficial effects of bariatric surgery. This review focuses on the most recent studies on the roles of bile acids and bile acid receptors Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 5 (TGR5) in bariatric surgery. We also discuss the possibility of modulating bile acid signaling as a pharmacological therapeutic approach to treating obesity and its associated metabolic complications.

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Mechanisms underlying weight loss and metabolic improvements in rodent models of bariatric surgery

Cited by 56 publications

References 116 publications

Sleeve gastrectomy leads to weight loss in the Magel2 knockout mouse

Sleeve gastrectomy leads to weight loss in the Magel2 knockout mouse

Weight loss independent changes in adipose tissue macrophage and T cell populations after sleeve gastrectomy in mice

Bile acid signaling and bariatric surgery

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