High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation andObesity in Mice via the TLR4 Signaling Pathway

Collection with item attached
2012
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/479857.do
DOI
10.1371/journal.pone.0047713
Title
High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation andObesity in Mice via the TLR4 Signaling Pathway
Description
This study was supported by a grant from World Class University Programthrough the National Research Foundation of Korea funded by the Ministryof Education, Science and Technology (R33-2008-000-10018-0). The fundershad no role in study design, data collection and analysis, decision topublish, or preparation of the manuscript.
abstract
Background & Aims: 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.
Methods: 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.
Results: 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-kappa B 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.
Conclusions: 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.
provenance
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language
English
author
Kim, Kyung-Ah
Gu, Wan
Lee, In-Ah
Joh, Eun-Ha
Kim, Dong-Hyun
accessioned
2018-09-28T13:10:35Z
available
2018-09-28T13:10:35Z
issued
2012
citation
PLOS ONE(7): 10
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/479857.do
Funder
교육과학기술부
Funding Program
2단계연구중심대학육성(0.5)
Project ID
1345196515
Jurisdiction
Rep.of Korea
Project Name
고령화사회대비 신약소재개발 사업단
rights
openAccess
type
article


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