'Creeping fat' Exacerbates Crohn’s Disease, New Study Reveals

Recent research has unveiled a surprising role of a specific type of fat called 'creeping fat' in worsening Crohn's disease. Traditionally regarded as a simple energy storage, fat tissue—also known as adipose tissue—actually partakes in complex hormonal, nervous, and immune signaling. A study conducted by Stanford Medicine and published in the journal Cell has demonstrated that creeping fat, an abnormal, stiff, finger-like deposit of fat encasing the intestines, actively contributes to the disease's progression.

Crohn's disease is a severe inflammatory bowel condition often diagnosed in teenagers and young adults. It features cycles of intestinal inflammation, leading to symptoms such as abdominal pain, diarrhea, weight loss, fatigue, and malnutrition. While anti-inflammatory drugs can provide relief, they frequently fall short in preventing complications like strictures—narrowing of the intestine caused by scar tissue—which can occur in up to 80% of untreated cases. Currently, surgery is often necessary to remove these strictures, but this is not a guaranteed long-term solution.

The study focused on understanding how creeping fat influences disease progression. Through analysis of tissue samples from Crohn's patients and animal models, researchers found that fibroblasts—cells involved in forming connective tissue—are present in creeping fat and are activated in response to mechanical tension and inflammation. These fibroblasts produce excess extracellular matrix, leading to scar tissue formation akin to the scarring seen in skin injuries. The findings suggest that creeping fat does not merely surround the damaged intestine but actively participates in fibrosis, promoting strictures.

The team also identified that disrupting specific signaling pathways, such as YAP/TAZ, in fibroblasts can reduce scar tissue formation. In mouse models, inhibiting these pathways resulted in fewer strictures, paving the way for potential new therapies aimed at preventing or delaying fibrosis in Crohn's disease.

The research challenges the traditional inside-out view of Crohn's disease, proposing a novel outside-in perspective. It highlights how inflammation and mechanical stress in the intestine activate creeping fat, which then signals back into the bowel to exacerbate tissue damage. These insights could revolutionize treatment approaches, shifting focus toward targeting fibrotic mechanisms rather than solely controlling inflammation.

This groundbreaking work underscores the importance of considering the role of adipose tissue in bowel diseases and offers hope for developing therapies that could prevent the need for repeated surgeries and improve the quality of life for Crohn's patients.