The Role of Adipose Tissue in the Pathogenesis and Therapeutic Outcomes of Inflammatory Bowel Disease

Abstract

Though historically regarded as an inert energy store, adipose tissue is a complex endocrine organ, which is increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD). Accumulating evidence points to visceral adipose tissue and specifically to its mesenteric component, or “creeping fat” as impacting on the disease course through its immunomodulatory properties. On the one hand, mesenteric fat acts as a physical barrier to inflammation and is involved in controlling host immune response to translocation of gut bacteria. On the other hand, however, there exists a strong link between visceral fat and complicated course of the disease with unfavorable therapeutic outcomes. Furthermore, “creeping fat” appears to play different roles in different IBD phenotypes, with the greatest pathogenetic contribution probably to an ileal form of Crohn’s disease. In this review, we summarize and discuss the existing literature on the subject and identify high-priority areas for future research. It may be that a better understanding of the role of mesenteric fat in IBD will determine new therapeutic targets and translate into improved clinical outcomes.

Role of Adipose Tissue in Inflammatory Bowel Disease

“…One retrospective review suggested that obese patients may have higher rates of perineal disease [ 25 ]; other studies found no differences in disease distribution or behavior for CD or UC patients [ 9 , 26 ]. These inconsistencies may be related to significant limitations of BMI as a biomarker of adiposity, as it is unable to differentiate between subcutaneous and visceral adipose tissue [ 27 ].…”

“…Adipose tissue is distributed in two main compartments, subcutaneous and visceral—see Figure 1 [ 27 , 34 ]. Exact differentiation of subcutaneous and visceral adipose tissue (VAT) is possible by abdominal magnetic resonance imaging or computed tomography used to measure the visceral fat area and subcutaneous fat area [ 15 , 35 ].…”

“…Fat wrapping was positively correlated with transmural inflammation, fibrosis, stricture formation, and macrophage and lymphocyte perivascular infiltration on histology [ 48 ]. The development of mesenteric creeping fat in CD has been hypothesized to be caused by adipocyte hyperplasia rather than hypertrophy [ 27 ], resulting in an approximately four-fold increase in the number of mesenteric adipocytes compared with healthy controls [ 41 ]. There are also some observations of edematous adipose tissue and enlarged lymph nodes in patients with UC undergoing an abdomino-perineal resection [ 3 ].…”

What Was First, Obesity or Inflammatory Bowel Disease? What Does the Gut Microbiota Have to Do with It?

“…Due to the fact that MAT is composed, in addition to adipocytes, of macrophages, after induction of monocyte chemoattractant protein-1 (MCP-1) expression, tissue infiltration by macrophages occurs. As a consequence, it may determine the severity of the disease and be a significant factor in pathogenesis [ 44 , 45 , 46 , 47 ]. More and more researchers draw attention to the link between leptin and IBD.…”

Changes in Anthropometric Parameters After Anti-TNFα Therapy in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

“…Evaluating the impact of anti-TNFα therapy on anthropometric parameter changes in patients with IBD is of particular importance as the increase in lean mass is beneficial (muscle representing the protein reserves of the body and contributing to improved immune function). This is especially true in patients with aggressive IBD in which lower BMI values may result from malnutrition accompanied with severe inflammation [ 7 ]. Nevertheless, about 15–40% of patients with IBD are obese, and an additional 20–40% are overweight [ 9 – 13 ], so the potential involvement of adipose tissue in intestinal inflammation and therapeutic outcomes has gained increasing attention [ 10 ].…”