Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance.
We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control d...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC5008778?pdf=render |
id |
doaj-d236c4ae016d4a1194d5722cb7078b94 |
---|---|
record_format |
Article |
spelling |
doaj-d236c4ae016d4a1194d5722cb7078b942020-11-25T01:38:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016193910.1371/journal.pone.0161939Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance.Rebecca E RinglingMichelle L GasteckiMakenzie L WoodfordKelly J Lum-NaiheRyan W GrantLakshmi PulakatVictoria J Vieira-PotterJaume PadillaWe tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis.http://europepmc.org/articles/PMC5008778?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rebecca E Ringling Michelle L Gastecki Makenzie L Woodford Kelly J Lum-Naihe Ryan W Grant Lakshmi Pulakat Victoria J Vieira-Potter Jaume Padilla |
spellingShingle |
Rebecca E Ringling Michelle L Gastecki Makenzie L Woodford Kelly J Lum-Naihe Ryan W Grant Lakshmi Pulakat Victoria J Vieira-Potter Jaume Padilla Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance. PLoS ONE |
author_facet |
Rebecca E Ringling Michelle L Gastecki Makenzie L Woodford Kelly J Lum-Naihe Ryan W Grant Lakshmi Pulakat Victoria J Vieira-Potter Jaume Padilla |
author_sort |
Rebecca E Ringling |
title |
Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance. |
title_short |
Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance. |
title_full |
Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance. |
title_fullStr |
Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance. |
title_full_unstemmed |
Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance. |
title_sort |
loss of nlrp3 does not protect mice from western diet-induced adipose tissue inflammation and glucose intolerance. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis. |
url |
http://europepmc.org/articles/PMC5008778?pdf=render |
work_keys_str_mv |
AT rebeccaeringling lossofnlrp3doesnotprotectmicefromwesterndietinducedadiposetissueinflammationandglucoseintolerance AT michellelgastecki lossofnlrp3doesnotprotectmicefromwesterndietinducedadiposetissueinflammationandglucoseintolerance AT makenzielwoodford lossofnlrp3doesnotprotectmicefromwesterndietinducedadiposetissueinflammationandglucoseintolerance AT kellyjlumnaihe lossofnlrp3doesnotprotectmicefromwesterndietinducedadiposetissueinflammationandglucoseintolerance AT ryanwgrant lossofnlrp3doesnotprotectmicefromwesterndietinducedadiposetissueinflammationandglucoseintolerance AT lakshmipulakat lossofnlrp3doesnotprotectmicefromwesterndietinducedadiposetissueinflammationandglucoseintolerance AT victoriajvieirapotter lossofnlrp3doesnotprotectmicefromwesterndietinducedadiposetissueinflammationandglucoseintolerance AT jaumepadilla lossofnlrp3doesnotprotectmicefromwesterndietinducedadiposetissueinflammationandglucoseintolerance |
_version_ |
1725055731769540608 |