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Increased Gut Permeability and Microbiota Change Associate with Mesenteric Fat Inflammation and Metabolic Dysfunction in Diet-Induced Obese Mice
Open accessAbstract
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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“Increased intestinal barrier permeability is related to the metabolic dysfunction of visceral adipose tissue (Lam et al., 2012).”
From Akkermansia muciniphila alleviates high‐fat‐diet ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Lam et al., 2012
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“Oscillibacter has been found to be associated with obesity (Xu et al., 2017), and its abundance is negatively correlated with intestinal barrier function (Lam et al., 2012).”
From Akkermansia muciniphila alleviates high‐fat‐diet ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Lam et al., 2012
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Metadata
- 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
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-03-23
- Volume
- 7
- Issue
- 3
- Pages
- e34233
- ISSN
- 1932-6203 (ISSN-L)
- 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
- 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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