Cited by 604Gut microbiota and healthAdipokines, Inflammation, and Metabolic DiseasesGastrointestinal motility and disorders

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Increased Gut Permeability and Microbiota Change Associate with Mesenteric Fat Inflammation and Metabolic Dysfunction in Diet-Induced Obese Mice

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Lam, Yan Y., 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.·2012·PLoS ONE

DOI 10.1371/journal.pone.0034233PMC PMC3311621

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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.

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Introducing mothur: Open-Source, Platform-Independent, Community-Supported Software for Describing and Comparing Microbial Communities
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Background
Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice
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Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability
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R Al-Sadi, 2010, IL-1[beta]-Induced Increase in Intestinal Epithelial Tight Junction Permeability Is Mediated by MEKK-1 Activation of Canonical NF-[kappa]B Pathway., The American Journal of Pathology, 177, 2310, 10.2353/ajpath.2010.100371 · DOI

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Is the enteric nervous system a lost piece of the gut-kidney axis puzzle linked to chronic kidney disease?
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Background
Effect of TU‐100 on Peyer's patches in a bacterial translocation rat model
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Self-citation
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“This may be due to other gut microbial metabolites altering the abundance of Oscillibacter _sp_1-3 strains, or it is possible that Oscillibacter _ sp_1-3 directly regulate the components that maintain the integrity of gut barrier function (46).”

Authors: Lam, Y. Y., Ha, C. W. Y., Campbell, C. R., Mitchell, A. J., Dinudom, A., Oscarsson, J., Cook, D. I., Hunt, N. H., Caterson, I. D., Holmes, A. J., & Storlien, L. H.
Affiliations: The University of Sydney (AU)
Corresponding author: Lam, Yan Y.
ORCID: Lam, Yan Y.
Ha, Connie W. Y.
Campbell, Craig R.
Mitchell, Andrew J.
Oscarsson, Jan
Hunt, Nicholas H.
Caterson, Ian D.
Holmes, Andrew J.
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2012-03-23
Volume: 7
Issue: 3
Pages: e34233
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0034233
PMC: PMC3311621
OpenAlex: W2000450805
Cited by: 604
References: 72
Citations by year: 2026: 24 · 2025: 33 · 2024: 39 · 2023: 58 · 2022: 62 · 2021: 59 · 2020: 58 · 2019: 53 · 2018: 44 · 2017: 41 · 2016: 41 · 2015: 34 · 2014: 29 · 2013: 21 · 2012: 8
FWCI: 11.84
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Figshare (submittedVersion, cc-by)
Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Funders: Medical Research Council
National Health and Medical Research Council (633240)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: diet-induced obesity, high saturated fat diet, intestinal permeability, gut microbiota, mesenteric fat inflammation, visceral adipose tissue, metabolic dysfunction, tight junctions, ZO-1, TNF-α, interleukin-6, adipose tissue macrophages, Lactobacillus, Oscillibacter, adiponectin, serum amyloid A
MeSH terms: Animals, Diet, Female, Inflammation, Intestinal Mucosa, Intestines, Mesentery, Mice, Inbred C57BL, Permeability, Mice

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Increased Gut Permeability and Microbiota Change Associate with Mesenteric Fat Inflammation and Metabolic Dysfunction in Diet-Induced Obese Mice

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