Ulcerative Colitis Resource Center

Ulcerative Colitis Resource Center

August 11, 2015
2 min read

'Creeping fat' may contribute to development, progression of IBD

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Intra-abdominal fat cells may play a role in the pathophysiology of inflammatory bowel disease, according to new research data.

“A well-appreciated feature of IBD, especially longstanding Crohn's disease, is intra-abdominal fat, also known as 'creeping fat,' which wraps around the intestine. However, it's not clear whether this fat is protective or harmful,” Charalabos Pothoulakis, MD, from the University of California, Los Angeles, said in a press release. “Our study offers insight into this phenomenon. We found that intra-abdominal fat cells may normally be programmed to dampen inflammation but, in fact, have acquired a tendency to promote inflammation in IBD.”

Pothoulakis and colleagues collected mesenteric fat tissues from 11 patients with ulcerative colitis, 11 with Crohn’s disease and 10 non-IBD controls, then isolated and cultured preadipocytes to evaluate the effect of the neuropeptide substance P on cytokine expression. They found that signaling mediators produced by the intra-abdominal fat cells from controls were significantly different compared with those from the IBD patients, which indicates these cells are actively involved in gut immunity and inflammation, according to the press release.

Increased expression of neurokinin-1 and -2 receptor mRNA was observed in IBD preadipocytes compared with controls, while increased expression of substance P mRNA was observed in ulcerative colitis preadipocytes compared with those from Crohn’s patients and controls.

The differences in the responses from intra-abdominal fat cells observed between Crohn’s and ulcerative colitis patients is “the first evidence that intra-abdominal fat tissue may be involved in the development of ulcerative colitis,” the release said.

The researchers also observed differential regulation of inflammatory mediator expression by substance P in IBD preadipocytes vs. controls, while Crohn’s and ulcerative colitis preadipocytes had disease-dependent responses to substance P. Thus, the study is also “the first to demonstrate differential disease-dependent responses in human fat cells to inflammatory mediators,” according to the release.

After exposure to substance P, interleukin (IL)-17A mRNA expression and release was also found to be increased in IBD preadipocytes, while IL-17 receptor A mRNA was increased in IBD colon biopsies.

“Fat represents a novel reserve of IL-17 during the disease and may affect the progress of IBD by altering intestinal responses via interactions with IL-17RA,” the researchers wrote. “This observation along with the identification of IL-17 as the most consistently regulated mediator in human mesenteric preadipocytes isolated from IBD patients in response to [substance P] suggests a potential role for this neuropeptide in the regulation of inflammatory changes in the intestine during IBD (both UC and Crohn’s disease) via modulation of IL-17 expression in the adjacent mesenteric preadipocytes. Furthermore, our observations introduce the preadipocytes as a novel cellular population with immune properties that are likely involved in the regulation of intestinal inflammation during IBD.”

“This research provides new insight that may lead to future targeting of intra-abdominal fat cells for therapeutic benefit,” Jerrold R. Turner, MD, PhD, AGAF, study co-author and editor-in-chief of  Cellular and Molecular Gastroenterology and Hepatology, said in the press release. by Adam Leitenberger

Disclosure: The researchers report no relevant financial disclosures.