“Metabolic Aspects” In Inflammatory Bowel Diseases

Arthur      Kaser; Herbert      Tilg

Abstract

Mesenteric fat hypertrophy is a common feature of inflammatory bowel diseases (IBD), especially Crohn´s disease. Although this “creeping fat” has been observed in the early days of this disease, its biological relevance is not understood. This adipose tissue has been recognized to release large amounts of various cytokines such as TNFa and adipocytokines such as adiponectin or leptin. Whereas leptin is definitely a pro-inflammatory adipocytokine, the role of the prototypic anti-inflammatory adipocytokine, namely adiponectin, in intestinal inflammation is less clear. Some experimental studies suggest that it could exert also pro-inflammatory activities in the gut. An important role for metabolic aspects and potentially adipocytokines has also come from recent studies demonstrating that ATG16L1- deficient mice show a strikingly enhanced expression of both adiponectin and leptin in epithelial cells. Autophagy not only plays a key role in intestinal inflammation, but is also involved in the regulation of lipid metabolism. Another recently identified pathway in IBD, namely endoplasmic stress/XBP1, regulates fatty acid synthesis and facilitates adipogenesis and adipocyte differentiataion. Therefore, XBP1 could possibly link intestinal inflammation with the development of “creeping fat” in Crohn’s disease. Metabolic aspects have evolved as of key importance in experimental colitis and human IBD, and certain adipocytokines, autophagy, and ER stress might reflect the central players.

Keywords: Adipocytokines, adiponectin, leptin, autophagy, XBP1, supported by the Christian Doppler Research Society, Inflammatory Bowel Diseases, C-C chemokine ligand