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.

Adiponectin confers protection from acute colitis and restricts a B cell immune response

“…These data are in agreement with other cellular stress systems where Adi-poR1 is necessary to reduce cellular damage and apoptosis (34,35). Importantly, it has been recently demonstrated that intracolonic injection of AdipoR1 siRNA worsens colitis in mice, thus reinforcing our observations (36). Taken together, these data suggest that APN through AdipoR1 is critical for maintaining IEC survival.…”

Insulin Production and Resistance in Different Models of Diet-Induced Obesity and Metabolic Syndrome

“…The frequent consumption of an empty-caloric diet, without physical activity, increases fat storage and results in obesity, hepatomegaly and T2DM [29]. Indeed, in the HF-EFr group, visceral fat was more pronounced and serum leptin levels were higher, similar to changes reported in patients [30]. Liver weight was highest in response to the HF-EFr-diet, and was associated with a significant progressive increase in intrahepatic triglyceride content as a result of expression of Fasn .…”

FABP4 blocker attenuates colonic hypomotility and modulates white adipose tissue‐derived hormone levels in mouse models mimicking constipation‐predominant IBS

“…insulin sensitivity), glucose metabolism, vascular and immune function making them key players in the pathogenesis of obesity, type 2 diabetes, metabolic syndrome, hypertension, atherosclerosis, inflammatory‐related diseases (e.g. inflammatory bowel disease) or colorectal cancer …”

“…inflammatory bowel disease) or colorectal cancer. [10][11][12][13][14][15][16] In recent years, much effort has been spent on uncovering the role of the fatty acid binding protein 4 (FABP4; aP2; AFABP), a small cytosolic protein (14-15 kDa) that is preferentially expressed in adipocytes and macrophages. Alterations in the expression of FABP4 have been implicated in the pathogenesis of obesity, metabolic syndrome, cardiovascular disease, and inflammation.…”