Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1

Aristea Sideri, Dimitris Stavrakis, Collin Bowe, David Q. Shih, Phillip Fleshner, Violeta Arsenescu, Razvan Arsenescu, Jerrold R. Turner, Charalabos Pothoulakis, Iordanes Karagiannides

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In inflammatory bowel disease (IBD), obesity is associated with worsening of the course of disease. Here, we examined the role of obesity in the development of colitis and studied mesenteric fat-epithelial cell interactions in patients with IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid (TNBS) colitis mouse model to create groups with obesity, colitis, and their combination. Changes in the mesenteric fat and intestine were assessed by histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR. Medium from human mesenteric fat and cultured preadipocytes was obtained from obese patients and those with IBD. Histological analysis showed inflammatory cell infiltrate and increased histological damage in the intestine and mesenteric fat of obese mice with colitis compared with all other groups. Obesity also increased the expression of proinflammatory cytokines including IL-1β, TNF-α, monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it decreased the TNBS-induced increases in IL-2 and IFN-γ in mesenteric adipose and intestinal tissues. Human mesenteric fat isolated from obese patients and those with and IBD demonstrated differential release of adipokines and growth factors compared with controls. Fat-conditioned media reduced adiponectin receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1 intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion, obesity worsens the outcome of experimental colitis, and obesity- and IBD-associated changes in adipose tissue promote differential mediator release in mesenteric fat that modulates colonocyte responses and may affect the course of colitis. Our results also suggest an important role for AdipoR1 for the fat-intestinal axis in the regulation of inflammation during colitis.

Original languageEnglish (US)
Pages (from-to)G591-G604
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume308
Issue number7
DOIs
StatePublished - Jan 1 2015

Fingerprint

Adiponectin Receptors
Colitis
Obesity
Fats
Cytokines
Inflammatory Bowel Diseases
Trinitrobenzenes
Sulfonic Acids
Intestines
Adipose Tissue
Epithelial Cells
Obese Mice
Adipokines
Chemokine CCL2
Conditioned Culture Medium
Interleukin-1
Adipocytes
Cell Communication
Peroxidase
Interleukin-2

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Sideri, Aristea ; Stavrakis, Dimitris ; Bowe, Collin ; Shih, David Q. ; Fleshner, Phillip ; Arsenescu, Violeta ; Arsenescu, Razvan ; Turner, Jerrold R. ; Pothoulakis, Charalabos ; Karagiannides, Iordanes. / Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2015 ; Vol. 308, No. 7. pp. G591-G604.
@article{7c014e643c7b497cab5303add2f22ec0,
title = "Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1",
abstract = "In inflammatory bowel disease (IBD), obesity is associated with worsening of the course of disease. Here, we examined the role of obesity in the development of colitis and studied mesenteric fat-epithelial cell interactions in patients with IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid (TNBS) colitis mouse model to create groups with obesity, colitis, and their combination. Changes in the mesenteric fat and intestine were assessed by histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR. Medium from human mesenteric fat and cultured preadipocytes was obtained from obese patients and those with IBD. Histological analysis showed inflammatory cell infiltrate and increased histological damage in the intestine and mesenteric fat of obese mice with colitis compared with all other groups. Obesity also increased the expression of proinflammatory cytokines including IL-1β, TNF-α, monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it decreased the TNBS-induced increases in IL-2 and IFN-γ in mesenteric adipose and intestinal tissues. Human mesenteric fat isolated from obese patients and those with and IBD demonstrated differential release of adipokines and growth factors compared with controls. Fat-conditioned media reduced adiponectin receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1 intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion, obesity worsens the outcome of experimental colitis, and obesity- and IBD-associated changes in adipose tissue promote differential mediator release in mesenteric fat that modulates colonocyte responses and may affect the course of colitis. Our results also suggest an important role for AdipoR1 for the fat-intestinal axis in the regulation of inflammation during colitis.",
author = "Aristea Sideri and Dimitris Stavrakis and Collin Bowe and Shih, {David Q.} and Phillip Fleshner and Violeta Arsenescu and Razvan Arsenescu and Turner, {Jerrold R.} and Charalabos Pothoulakis and Iordanes Karagiannides",
year = "2015",
month = "1",
day = "1",
doi = "10.1152/ajpgi.00269.2014",
language = "English (US)",
volume = "308",
pages = "G591--G604",
journal = "American Journal of Physiology - Gastrointestinal and Liver Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "7",

}

Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1. / Sideri, Aristea; Stavrakis, Dimitris; Bowe, Collin; Shih, David Q.; Fleshner, Phillip; Arsenescu, Violeta; Arsenescu, Razvan; Turner, Jerrold R.; Pothoulakis, Charalabos; Karagiannides, Iordanes.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 308, No. 7, 01.01.2015, p. G591-G604.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1

AU - Sideri, Aristea

AU - Stavrakis, Dimitris

AU - Bowe, Collin

AU - Shih, David Q.

AU - Fleshner, Phillip

AU - Arsenescu, Violeta

AU - Arsenescu, Razvan

AU - Turner, Jerrold R.

AU - Pothoulakis, Charalabos

AU - Karagiannides, Iordanes

PY - 2015/1/1

Y1 - 2015/1/1

N2 - In inflammatory bowel disease (IBD), obesity is associated with worsening of the course of disease. Here, we examined the role of obesity in the development of colitis and studied mesenteric fat-epithelial cell interactions in patients with IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid (TNBS) colitis mouse model to create groups with obesity, colitis, and their combination. Changes in the mesenteric fat and intestine were assessed by histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR. Medium from human mesenteric fat and cultured preadipocytes was obtained from obese patients and those with IBD. Histological analysis showed inflammatory cell infiltrate and increased histological damage in the intestine and mesenteric fat of obese mice with colitis compared with all other groups. Obesity also increased the expression of proinflammatory cytokines including IL-1β, TNF-α, monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it decreased the TNBS-induced increases in IL-2 and IFN-γ in mesenteric adipose and intestinal tissues. Human mesenteric fat isolated from obese patients and those with and IBD demonstrated differential release of adipokines and growth factors compared with controls. Fat-conditioned media reduced adiponectin receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1 intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion, obesity worsens the outcome of experimental colitis, and obesity- and IBD-associated changes in adipose tissue promote differential mediator release in mesenteric fat that modulates colonocyte responses and may affect the course of colitis. Our results also suggest an important role for AdipoR1 for the fat-intestinal axis in the regulation of inflammation during colitis.

AB - In inflammatory bowel disease (IBD), obesity is associated with worsening of the course of disease. Here, we examined the role of obesity in the development of colitis and studied mesenteric fat-epithelial cell interactions in patients with IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid (TNBS) colitis mouse model to create groups with obesity, colitis, and their combination. Changes in the mesenteric fat and intestine were assessed by histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR. Medium from human mesenteric fat and cultured preadipocytes was obtained from obese patients and those with IBD. Histological analysis showed inflammatory cell infiltrate and increased histological damage in the intestine and mesenteric fat of obese mice with colitis compared with all other groups. Obesity also increased the expression of proinflammatory cytokines including IL-1β, TNF-α, monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it decreased the TNBS-induced increases in IL-2 and IFN-γ in mesenteric adipose and intestinal tissues. Human mesenteric fat isolated from obese patients and those with and IBD demonstrated differential release of adipokines and growth factors compared with controls. Fat-conditioned media reduced adiponectin receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1 intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion, obesity worsens the outcome of experimental colitis, and obesity- and IBD-associated changes in adipose tissue promote differential mediator release in mesenteric fat that modulates colonocyte responses and may affect the course of colitis. Our results also suggest an important role for AdipoR1 for the fat-intestinal axis in the regulation of inflammation during colitis.

UR - http://www.scopus.com/inward/record.url?scp=84929645844&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929645844&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00269.2014

DO - 10.1152/ajpgi.00269.2014

M3 - Article

C2 - 25591865

AN - SCOPUS:84929645844

VL - 308

SP - G591-G604

JO - American Journal of Physiology - Gastrointestinal and Liver Physiology

JF - American Journal of Physiology - Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 7

ER -