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

• Published in: PloS one 2011-07, Vol.6 (7), p.e22978
• Main Authors: Mencarelli, Andrea, Distrutti, Eleonora, Renga, Barbara, D'Amore, Claudio, Cipriani, Sabrina, Palladino, Giuseppe, Donini, Annibale, Ricci, Patrizia, Fiorucci, Stefano
• Format: Article
• Language: English
• Subjects: Adipocytes; Adiponectin; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adult; Animals; Anorexia; Biology; Blotting, Western; Body fat; Cells, Cultured; Colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis - metabolism; Colon; Colon cancer; Crohn's Disease; Crohns disease; Cytochrome; Cytokines - metabolism; Development and progression; Diabetes; Enzyme-Linked Immunosorbent Assay; Explants; Female; Heart failure; Humans; Immunity; Immunoenzyme Techniques; Inflammation; Inflammation - physiopathology; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory response; Interleukin 6; Intestine; Intestines - metabolism; Intestines - pathology; Leptin; Liver; Liver diseases; Liver X Receptors; Lymphatic system; Male; Medical research; Medicine; Mesentery - metabolism; Mesentery - pathology; Metabolism; Metabolites; Mice; Neural networks; Nuclear receptors; Obesity; Orphan Nuclear Receptors - genetics; Orphan Nuclear Receptors - metabolism; Pathogenesis; Patients; Peroxisome proliferator-activated receptors; PPAR gamma - genetics; PPAR gamma - metabolism; Probiotics; Probiotics - therapeutic use; Receptor mechanisms; Receptors; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Steroid - genetics; Receptors, Steroid - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Rodents; Signal Transduction; Signs and symptoms; Surgery; Tissues; Transcription, Genetic; Trinitrobenzenesulfonic Acid - toxicity; Tumor necrosis factor-α; Weight control; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022978

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. 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. 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. Probiotic administration attenuated development of signs and symptoms of colitis, reduced colonic expression of TNFα, IL-6 and IFNγ and reserved colonic downregulation of PPARγ, PXR and FXR caused by TNBS. Mesenteric fat depots isolated from TNBS-treated animals had increased expression of inflammatory mediators along with PPARγ, 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 PPARγ and FXR with both tissue expressing high levels of leptin. Exposure of these tissues to VSL#3 medium abrogates leptin release. Mesenteric adipose tissue from rodent colitis and Crohn's disease is metabolically active and shows inflammation-driven regulation of PPARγ, FXR and leptin. Probiotics correct the inflammation-driven metabolic dysfunction.