02/04/2025
Creeping fat found to cause intestinal lining thickening in Crohn’s disease
A team of Cleveland Clinic researchers is among the first to confirm creeping fat as a novel contributor to intestinal stricture formation in Crohn’s disease.
The Gastroenterology study examined human tissue samples and found that the presence of creeping fat is linked to thickening of the muscle that surrounds the gut when the gut is inflamed. The Rieder lab removed the creeping fat in a preclinical model of Crohn’s disease and the intestinal muscle did not thicken. Further examination found that the creeping fat produces free fatty acids which activate the muscle cells, causing their increase in numbers and thickening of the muscle layer.
“The association between creeping fat and Crohn’s disease has been known for a very long time, but we did not know how exactly the two were connected,” says Florian Rieder, MD, a gastroenterologist and senior author of the study. “What we've provided is one piece of evidence that creeping fat plays an important role for the muscle thickness that you find in stricturing diseases like Crohn’s.”
Crohn’s disease has been a known condition for almost 100 years, but only a fraction of Crohn’s disease patients find relief from medications currently on the market. In 2020, Dr. Rieder was awarded a 5-year, $2 million grant from the National Institutes of Health to explore new causes of intestinal strictures and their link to the development of creeping fat in patients with Crohn’s disease. Creeping fat is a type of mesenteric fat that surrounds the blood vessels and lymph nodes that supply the small intestine (separate from obesity). Creeping fat wrapped around an inflamed gut is a hallmark of Crohn’s disease, but until now its biology was not well understood.
New opportunities for intestinal stricture research
There are no specific anti-stricture therapies available, despite most patients with Crohn’s disease developing symptomatic intestinal strictures. Dr. Rieder explains his team’s discovery can support new therapies in two ways: confirming that the creeping fat is harmful and providing a target for inhibitors. The lab’s next step is to investigate the long-chain fatty acid (FA) transporter carnitine palmitoyltransferase (CPT)1A identified in the study to see if inhibiting it prevents strictures.
“We really don’t know why some patients respond better to specific types of medications than others. We tend to cycle through different types of therapy to control inflammation to see what works best,” Dr. Rieder explains. “It’s not the best approach for the patient, and that’s something I’m trying to change with my work in the lab.”
And there’s still more to learn about creeping fat. Dr. Rieder is optimistic that this new study will prompt the Crohn’s research community to focus on further studies on the role of muscle in Crohn’s disease. His lab plans to conduct additional studies looking at preventing thickening of the muscle in response to gut inflammation.
“I hope that by showing the functional link between creeping fat and strictures, others will develop an interest in it and focus on these interactions of the creeping fat with the intestine — there is a lot of potential in finding therapies in that space, and at the interface of the fat and the muscle,” Dr. Rieder says.
