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Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation.


ABSTRACT:

Background

Adipocytes from mesenteric white adipose tissue amplify the inflammatory response and participate in inflammation-driven immune dysfunction in Crohn's disease by releasing proinflammatory mediators. Peroxisome proliferator-activated receptors (PPAR)-? and -?, pregnane x receptor (PXR), farnesoid x receptor (FXR) and liver x-receptor (LXR) are ligand-activated nuclear receptor that provide counter-regulatory signals to dysregulated immunity and modulates adipose tissue.

Aims

To investigate the expression and function of nuclear receptors in intestinal and adipose tissues in a rodent model of colitis and mesenteric fat from Crohn's patients and to investigate their modulation by probiotics.

Methods

Colitis was induced by TNBS administration. Mice were administered vehicle or VSL#3, daily for 10 days. Abdominal fat explants obtained at surgery from five Crohn's disease patients and five patients with colon cancer were cultured with VSL#3 medium.

Results

Probiotic administration attenuated development of signs and symptoms of colitis, reduced colonic expression of TNF?, IL-6 and IFN? and reserved colonic downregulation of PPAR?, PXR and FXR caused by TNBS. Mesenteric fat depots isolated from TNBS-treated animals had increased expression of inflammatory mediators along with PPAR?, FXR, leptin and adiponectin. These changes were prevented by VSL#3. Creeping fat and mesenteric adipose tissue from Crohn's patients showed a differential expression of PPAR? and FXR with both tissue expressing high levels of leptin. Exposure of these tissues to VSL#3 medium abrogates leptin release.

Conclusions

Mesenteric adipose tissue from rodent colitis and Crohn's disease is metabolically active and shows inflammation-driven regulation of PPAR?, FXR and leptin. Probiotics correct the inflammation-driven metabolic dysfunction.

SUBMITTER: Mencarelli A 

PROVIDER: S-EPMC3146529 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation.

Mencarelli Andrea A   Distrutti Eleonora E   Renga Barbara B   D'Amore Claudio C   Cipriani Sabrina S   Palladino Giuseppe G   Donini Annibale A   Ricci Patrizia P   Fiorucci Stefano S  

PloS one 20110729 7


<h4>Background</h4>Adipocytes from mesenteric white adipose tissue amplify the inflammatory response and participate in inflammation-driven immune dysfunction in Crohn's disease by releasing proinflammatory mediators. Peroxisome proliferator-activated receptors (PPAR)-α and -γ, pregnane x receptor (PXR), farnesoid x receptor (FXR) and liver x-receptor (LXR) are ligand-activated nuclear receptor that provide counter-regulatory signals to dysregulated immunity and modulates adipose tissue.<h4>Aims  ...[more]

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