This review explores how mesenteric adipose tissue, particularly creeping fat, contributes to intestinal inflammation through dysregulated adipokine signalling. We explore how metabolic stress alters immune-adipose interactions and promotes disease progression. Insights from mechanistic studies highlight mesenteric adipose tissue as a key driver of inflammation and a potential therapeutic target.
ABSTRACT
Inflammatory bowel disease, including Crohn’s disease (CD) and ulcerative colitis, is becoming increasingly prevalent. Obesity, specifically visceral adiposity, has been identified as a significant risk factor for disease recurrence and complications. A hallmark of CD is the development of “creeping fat”, which is characterized by adipocyte hyperplasia and increased adipokine secretion. Under homeostatic conditions, adipose tissue plays a key role in immune regulation through the secretion of adipokines, such as leptin and adiponectin, which modulate JAK/STAT, AMPK, and NF-kB pathways in immune and epithelial cells. However, in obesity and under metabolic stress, mesenteric adipose tissue undergoes immune remodelling marked by macrophage polarization, Th1/Th17 differentiation, and fibroblast reprogramming driven by TNFα, IL-6, and TGF-β1. These changes promote sustained cytokine production, extracellular matrix deposition, and fibrostenotic remodelling of the intestinal wall. This review highlights current evidence linking mesenteric adipose tissue and creeping fat immunometabolism to intestinal inflammation in CD. We outline key cellular and signalling mechanisms that connect mesenteric adipose to mucosal immune dysregulation and discuss emerging experimental models.