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PMID: 22457829 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice.

PloS one ·Vol. 7 ·No. 3 ·2012-00-00 ·Pages e34233

Lam YY, Ha CW, Campbell CR, Mitchell AJ, Dinudom A, Oscarsson J, Cook DI, Hunt NH, Caterson ID, Holmes AJ, Storlien LH

Abstract

We investigated the relationship between gut health, visceral fat dysfunction and metabolic disorders in diet-induced obesity. C57BL/6J mice were fed control or high saturated fat diet (HFD). Circulating glucose, insulin and inflammatory markers were measured. Proximal colon barrier function was assessed by measuring transepithelial resistance and mRNA expression of tight-junction proteins. Gut microbiota profile was determined by 16S rDNA pyrosequencing. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA levels were measured in proximal colon, adipose tissue and liver using RT-qPCR. Adipose macrophage infiltration (F4/80⁺) was assessed using immunohistochemical staining. HFD mice had a higher insulin/glucose ratio (P = 0.020) and serum levels of serum amyloid A3 (131%; P = 0.008) but reduced circulating adiponectin (64%; P = 0.011). In proximal colon of HFD mice compared to mice fed the control diet, transepithelial resistance and mRNA expression of zona occludens 1 were reduced by 38% (P<0.001) and 40% (P = 0.025) respectively and TNF-α mRNA level was 6.6-fold higher (P = 0.037). HFD reduced Lactobacillus (75%; P<0.001) but increased Oscillibacter (279%; P = 0.004) in fecal microbiota. Correlations were found between abundances of Lactobacillus (r = 0.52; P = 0.013) and Oscillibacter (r = -0.55; P = 0.007) with transepithelial resistance of the proximal colon. HFD increased macrophage infiltration (58%; P = 0.020), TNF-α (2.5-fold, P<0.001) and IL-6 mRNA levels (2.5-fold; P = 0.008) in mesenteric fat. Increased macrophage infiltration in epididymal fat was also observed with HFD feeding (71%; P = 0.006) but neither TNF-α nor IL-6 was altered. Perirenal and subcutaneous adipose tissue showed no signs of inflammation in HFD mice. The current results implicate gut dysfunction, and attendant inflammation of contiguous adipose, as salient features of the metabolic dysregulation of diet-induced obesity.

MeSH Terms
Animals Diet Female Inflammation/metabolism,pathology Intestinal Mucosa/metabolism Intestines/microbiology,physiopathology Mesentery/metabolism,pathology Mice Mice, Inbred C57BL Permeability
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Lam Yan Y
Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Sydney, Australia. [email protected]
Ha Connie W Y
Campbell Craig R
Mitchell Andrew J
Dinudom Anuwat
Oscarsson Jan
Cook David I
Hunt Nicholas H
Caterson Ian D
Holmes Andrew J
Storlien Len H
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0034233
Email
[email protected]
Published
2012-00-00
Epub
2012-00-23
Pages
e34233
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3311621
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0034233 PMC Full Text View journal details
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