High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway.
While it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3473013?pdf=render |
id |
doaj-f6a617cc7b034b81945f969c7bd5de21 |
---|---|
record_format |
Article |
spelling |
doaj-f6a617cc7b034b81945f969c7bd5de212020-11-25T01:30:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4771310.1371/journal.pone.0047713High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway.Kyung-Ah KimWan GuIn-Ah LeeEun-Ha JohDong-Hyun KimWhile it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a high-fat diet.C57BL/6J and TLR4-deficient C57BL/10ScNJ mice were maintained on a low-fat (10 kcal % fat) diet (LFD) or a high-fat (60 kcal % fat) diet (HFD) for 8 weeks.HFD induced macrophage infiltration and inflammation in the adipose tissue, as well as an increase in the circulating proinflammatory cytokines. HFD increased both plasma and fecal endotoxin levels and resulted in dysregulation of the gut microbiota by increasing the Firmicutes to Bacteriodetes ratio. HFD induced the growth of Enterobecteriaceae and the production of endotoxin in vitro. Furthermore, HFD induced colonic inflammation, including the increased expression of proinflammatory cytokines, the induction of Toll-like receptor 4 (TLR4), iNOS, COX-2, and the activation of NF-κB in the colon. HFD reduced the expression of tight junction-associated proteins claudin-1 and occludin in the colon. HFD mice demonstrated higher levels of Akt and FOXO3 phosphorylation in the colon compared to the LFD mice. While the body weight of HFD-fed mice was significantly increased in both TLR4-deficient and wild type mice, the epididymal fat weight and plasma endotoxin level of HFD-fed TLR4-deficient mice were 69% and 18% of HFD-fed wild type mice, respectively. Furthermore, HFD did not increase the proinflammatory cytokine levels in TLR4-deficient mice.HFD induces inflammation by increasing endotoxin levels in the intestinal lumen as well as in the plasma by altering the gut microbiota composition and increasing its intestinal permeability through the induction of TLR4, thereby accelerating obesity.http://europepmc.org/articles/PMC3473013?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kyung-Ah Kim Wan Gu In-Ah Lee Eun-Ha Joh Dong-Hyun Kim |
spellingShingle |
Kyung-Ah Kim Wan Gu In-Ah Lee Eun-Ha Joh Dong-Hyun Kim High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS ONE |
author_facet |
Kyung-Ah Kim Wan Gu In-Ah Lee Eun-Ha Joh Dong-Hyun Kim |
author_sort |
Kyung-Ah Kim |
title |
High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. |
title_short |
High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. |
title_full |
High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. |
title_fullStr |
High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. |
title_full_unstemmed |
High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. |
title_sort |
high fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the tlr4 signaling pathway. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
While it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a high-fat diet.C57BL/6J and TLR4-deficient C57BL/10ScNJ mice were maintained on a low-fat (10 kcal % fat) diet (LFD) or a high-fat (60 kcal % fat) diet (HFD) for 8 weeks.HFD induced macrophage infiltration and inflammation in the adipose tissue, as well as an increase in the circulating proinflammatory cytokines. HFD increased both plasma and fecal endotoxin levels and resulted in dysregulation of the gut microbiota by increasing the Firmicutes to Bacteriodetes ratio. HFD induced the growth of Enterobecteriaceae and the production of endotoxin in vitro. Furthermore, HFD induced colonic inflammation, including the increased expression of proinflammatory cytokines, the induction of Toll-like receptor 4 (TLR4), iNOS, COX-2, and the activation of NF-κB in the colon. HFD reduced the expression of tight junction-associated proteins claudin-1 and occludin in the colon. HFD mice demonstrated higher levels of Akt and FOXO3 phosphorylation in the colon compared to the LFD mice. While the body weight of HFD-fed mice was significantly increased in both TLR4-deficient and wild type mice, the epididymal fat weight and plasma endotoxin level of HFD-fed TLR4-deficient mice were 69% and 18% of HFD-fed wild type mice, respectively. Furthermore, HFD did not increase the proinflammatory cytokine levels in TLR4-deficient mice.HFD induces inflammation by increasing endotoxin levels in the intestinal lumen as well as in the plasma by altering the gut microbiota composition and increasing its intestinal permeability through the induction of TLR4, thereby accelerating obesity. |
url |
http://europepmc.org/articles/PMC3473013?pdf=render |
work_keys_str_mv |
AT kyungahkim highfatdietinducedgutmicrobiotaexacerbatesinflammationandobesityinmiceviathetlr4signalingpathway AT wangu highfatdietinducedgutmicrobiotaexacerbatesinflammationandobesityinmiceviathetlr4signalingpathway AT inahlee highfatdietinducedgutmicrobiotaexacerbatesinflammationandobesityinmiceviathetlr4signalingpathway AT eunhajoh highfatdietinducedgutmicrobiotaexacerbatesinflammationandobesityinmiceviathetlr4signalingpathway AT donghyunkim highfatdietinducedgutmicrobiotaexacerbatesinflammationandobesityinmiceviathetlr4signalingpathway |
_version_ |
1725088563911983104 |