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

OBJECTIVE: Obesity is associated with low-grade chronic inflammation. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery would reduce activation of the NLRP3 inflammasome in metabolically active adipose tissue (AT) of obese rats, and this change would be related to decreases in body weight...

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Autores principales: Mocanu, Andreea Oana, Mulya, Anny, Huang, Hazel, Dan, Olivia, Shimizu, Hideharu, Batayyah, Esam, Brethauer, Stacy A., Dinischiotu, Anca, Kirwan, John P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593548/
https://www.ncbi.nlm.nih.gov/pubmed/26437377
http://dx.doi.org/10.1371/journal.pone.0139764
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author Mocanu, Andreea Oana
Mulya, Anny
Huang, Hazel
Dan, Olivia
Shimizu, Hideharu
Batayyah, Esam
Brethauer, Stacy A.
Dinischiotu, Anca
Kirwan, John P.
author_facet Mocanu, Andreea Oana
Mulya, Anny
Huang, Hazel
Dan, Olivia
Shimizu, Hideharu
Batayyah, Esam
Brethauer, Stacy A.
Dinischiotu, Anca
Kirwan, John P.
author_sort Mocanu, Andreea Oana
collection PubMed
description OBJECTIVE: Obesity is associated with low-grade chronic inflammation. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery would reduce activation of the NLRP3 inflammasome in metabolically active adipose tissue (AT) of obese rats, and this change would be related to decreases in body weight and improved glycemic control. METHODS: Omental, mesenteric and subcutaneous fat depots were collected from Sprague-Dawley rats: Sham control and RYGB; 90-days after surgery. NLRP3, caspase–1, apoptosis-associated speck-like protein (ASC), IL–1β, IL–18, IL–6 and MCP–1 gene and protein expression were quantified. Glucose metabolism was assessed by oral glucose tolerance test (OGTT). RESULTS: Compared to Sham surgery controls, RYGB surgery decreased IL–6, MCP–1, NLRP3, IL–18, caspase–1 and ASC in omental fat, and decreased IL–6, MCP1, IL–1β, IL–18, caspase–1 and ASC gene expression in mesenteric fat. We observed differential gene expression between visceral and subcutaneous fat for IL–6 and IL–1β, both being downregulated by RYGB in visceral, and upregulated in subcutaneous depots. These changes in gene expression were accompanied by a decrease in NLRP3, ASC, IL–18, caspase–1 and IL–1β protein expression in omental tissue. We found a positive correlation between caspase–1, ASC, MCP–1, IL–18 and IL–6 gene expression following surgery and glucose AUC response in omental fat, while the change in glucose AUC response correlated with caspase–1 gene expression in subcutaneous fat. CONCLUSION: This study demonstrates that bariatric surgery reverses inflammation in visceral adipose tissue by suppressing NLRP3 inflammasome activation. These are the first data to implicate the NLRP3 inflammasome in diabetes remission after RYGB surgery.
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spelling pubmed-45935482015-10-14 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, Hideharu Batayyah, Esam Brethauer, Stacy A. Dinischiotu, Anca Kirwan, John P. PLoS One Research Article OBJECTIVE: Obesity is associated with low-grade chronic inflammation. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery would reduce activation of the NLRP3 inflammasome in metabolically active adipose tissue (AT) of obese rats, and this change would be related to decreases in body weight and improved glycemic control. METHODS: Omental, mesenteric and subcutaneous fat depots were collected from Sprague-Dawley rats: Sham control and RYGB; 90-days after surgery. NLRP3, caspase–1, apoptosis-associated speck-like protein (ASC), IL–1β, IL–18, IL–6 and MCP–1 gene and protein expression were quantified. Glucose metabolism was assessed by oral glucose tolerance test (OGTT). RESULTS: Compared to Sham surgery controls, RYGB surgery decreased IL–6, MCP–1, NLRP3, IL–18, caspase–1 and ASC in omental fat, and decreased IL–6, MCP1, IL–1β, IL–18, caspase–1 and ASC gene expression in mesenteric fat. We observed differential gene expression between visceral and subcutaneous fat for IL–6 and IL–1β, both being downregulated by RYGB in visceral, and upregulated in subcutaneous depots. These changes in gene expression were accompanied by a decrease in NLRP3, ASC, IL–18, caspase–1 and IL–1β protein expression in omental tissue. We found a positive correlation between caspase–1, ASC, MCP–1, IL–18 and IL–6 gene expression following surgery and glucose AUC response in omental fat, while the change in glucose AUC response correlated with caspase–1 gene expression in subcutaneous fat. CONCLUSION: This study demonstrates that bariatric surgery reverses inflammation in visceral adipose tissue by suppressing NLRP3 inflammasome activation. These are the first data to implicate the NLRP3 inflammasome in diabetes remission after RYGB surgery. Public Library of Science 2015-10-05 /pmc/articles/PMC4593548/ /pubmed/26437377 http://dx.doi.org/10.1371/journal.pone.0139764 Text en © 2015 Mocanu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mocanu, Andreea Oana
Mulya, Anny
Huang, Hazel
Dan, Olivia
Shimizu, Hideharu
Batayyah, Esam
Brethauer, Stacy A.
Dinischiotu, Anca
Kirwan, John P.
Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats
title Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats
title_full Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats
title_fullStr Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats
title_full_unstemmed Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats
title_short Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats
title_sort effect of roux-en-y gastric bypass on the nlrp3 inflammasome in adipose tissue from obese rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593548/
https://www.ncbi.nlm.nih.gov/pubmed/26437377
http://dx.doi.org/10.1371/journal.pone.0139764
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