Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats

Mocanu, Andreea Oana; Mulya, Anny; Huang, Hazel; Dan, Olivia; Shimizu, Hiroki; Batayyah, Esam; Brethauer, Stacy A.; Dinischiotu, Anca; Kirwan, John P.

doi:10.1371/journal.pone.0139764

Cited by 28 publications

(20 citation statements)

References 38 publications

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“…A reduction in chronic low grade inflammation has the potential to greatly attenuate insulin resistance and represents a potentially powerful mechanism for reestablishing glycemic status in these patients. We have previously shown that bariatric surgery improves glucose tolerance in obese rats and this effect is mediated through the NLRP3 inflammasome [6]. However, the effect was observed in adipose tissue and the animals were obese and insulin resistant, but did not have diabetes per se.…”

Section: Discussionmentioning

confidence: 99%

“…The inflammasome is a multiprotein oligomer that plays a key role in activation of inflammatory pathways involved in the development of insulin resistance [3] and the pathogenesis of T2D [4, 5]. We have previously shown that bariatric surgery reverses inflammation in visceral adipose tissue from obese, non-diabetic rats, by suppressing activation of the NOD-like receptor family, pyrin domain containing-3 (NLRP3) inflammasome [6]. NLRP3 is a pattern recognition receptor that forms a multiprotein inflammasome complex and initiates the inflammatory response [4, 5].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Pancreatic Islets from Zucker Diabetic Fatty Rats

et al. 2016

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Purpose Diabetes and obesity are associated with inflammasome-mediated low-grade, chronic inflammation that may induce pancreatic beta-cell dysfunction and apoptosis. We examined the effects of Roux-en-Y gastric bypass (RYGB) surgery on NOD-like receptor family, pyrin domain containing-3 (NLRP3) inflammasome-related genes from pancreatic islets of Zucker diabetic fatty rats. Materials and Methods Islets were collected from Zucker diabetic fatty sham control and RYGB, 30 days after surgery. We assessed expression of genes that regulate glucose metabolism and the NLRP3 inflammasome (NLRP3, caspase-1, IL-1β, IL-18, apoptosis-associated speck-like protein), IL-6, and monocyte chemoattractant protein-1. Results Gene expression for NLRP3 (p < 0.02), IL-1β (p < 0.04), and IL-6 (p < 0.01) was reduced by RYGB and positively correlated with change in body weight. IL-1β positively correlated with glucose AUC response. Conclusion Suppression of the NLRP3 inflammasome in pancreatic islets may contribute to improved glycemic control after RYGB.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Pancreatic Islets from Zucker Diabetic Fatty Rats

et al. 2016

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“…The protocol was approved and performed in compliance with the Cleveland Clinic Institutional Animal Care and Use Committee (IACUC), as noted previously (Mocanu et al. ; Mosinski et al. ).…”

Section: Methodsmentioning

confidence: 99%

“…The protocol was approved and performed in compliance with the Cleveland Clinic Institutional Animal Care and Use Committee (IACUC), as noted previously (Mocanu et al 2015;Mosinski et al 2016). Briefly, sixteen 12week-old SD rats (Charles River Laboratories, Wilmington, MA) were housed individually in a 12-h light/dark cycle under constant ambient temperature (21-23°C) and humidity.…”

Section: Animal Care and Surgical Interventionmentioning

confidence: 99%

Effect of Roux-en-Y gastric bypass on liver mitochondrial dynamics in a rat model of obesity

et al. 2018

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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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“…According to the World Health Organization, the prevalence of diabetes worldwide will reach 334 million people (2) and therefore it poses a serious threat to human health. Diabetes typically results from hyperglycaemia due to insulin resistance and a relative lack of insulin; the majority of the increased risk of mortality is attributable to associated macrovascular atherosclerotic diseases (3,4). Out of all patients with diabetes, >90% have type 2 diabetes mellitus (T2DM) (5).…”

Section: Introductionmentioning

confidence: 99%

Effect of gastric bypass combined with ileal transportation on type 2 diabetes mellitus

et al. 2018

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Abstract. Type 2 diabetes mellitus (T2DM) is a chronic progressive disease, which manifests as an endocrine disorder. Among the different methods of surgery available to treat patients with T2DM, Roux-en-Y gastric bypass (RYGBP) and ileal transposition (IT) are the most commonly performed. The aim of the present study was to investigate the effects of RYGBP combined with IT on rats with T2DM. A total of 8 healthy male rats were used as a control group and 40 GK rats were randomly divided into 5 groups: A diabetes mellitus (DM) group, a sham operative group (SO), a RYGBP group, an IT group and a RYGBP+IT group. The results demonstrated that fasting blood glucose, triglyceride, total cholesterol and gastric inhibitory polypeptide levels in all treatment groups were significantly lower than those of the SO and DM groups. Furthermore, levels TC and TG in the RYGBP+IT group were significantly lower than in the RYGBP and IT groups. Levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase mRNA and IRS-2 protein in all treatment groups were also significantly lower than those of the SO group; and they were significantly lower in the RYGBP+IT group compared with the RYGBP and IT groups. The expression of phosphorylated Akt in the treatment groups was significantly higher than the SO group and was significantly higher in the RYGBP+IT group compared with the RYGBP and IT groups. These results indicate that RYGBP and IT surgical treatment can induce T2DM remission by mediating the expression of insulin-related factors to reverse insulin resistance. The current study also indicated that the effect of RYGBP combined with IT may be developed as a novel first-line method of treating T2DM.

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Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats

Cited by 28 publications

References 38 publications

Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Pancreatic Islets from Zucker Diabetic Fatty Rats

Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Pancreatic Islets from Zucker Diabetic Fatty Rats

Effect of Roux-en-Y gastric bypass on liver mitochondrial dynamics in a rat model of obesity

Effect of gastric bypass combined with ileal transportation on type 2 diabetes mellitus

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