title: Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biochemistry Department, Faculty of Biology, University of Bucharest, Bucharest, Romania; Metabolic Translational Research Center, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Andreea Oana
authors.initials: AO
authors.lastname: Mocanu
authors.affiliation: Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Anny
authors.initials: A
authors.lastname: Mulya
authors.affiliation: Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Hazel
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Bariatric Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Olivia
authors.initials: O
authors.lastname: Dan
authors.affiliation: Department of Bariatric Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of Bariatric Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Esam
authors.initials: E
authors.lastname: Batayyah
authors.affiliation: Department of Bariatric Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Stacy A
authors.initials: SA
authors.lastname: Brethauer
authors.affiliation: Biochemistry Department, Faculty of Biology, University of Bucharest, Bucharest, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Dinischiotu
authors.affiliation: Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio, United States of America; Department of Gastroenterology & Hepatology, Cleveland Clinic, Cleveland, Ohio, United States of America; Metabolic Translational Research Center, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D015390:Gastric Bypass; D005951:Glucose Tolerance Test; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009765:Obesity / Q000378:metabolism* / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D020170:Caspase 1