Adipokines and Their Role in Intestinal Inflammation

Abstract

Fat tissue was initially described for its endocrine and metabolic function. Over the last two decades increasing evidence indicated a close interaction with the immune system. Partly responsible for this immune modulatory function are soluble factors released by the fat tissue, most prominently the so-called adipokines. These discoveries led to the question how adipokines influence inflammatory diseases. Linking inflammation and adipose tissue, Crohn's disease, a chronic inflammatory bowel disease, is of particular interest for studying the immune modulatory properties of adipokines since it is characterized by a hyperplasia of the mesenteric fat that subsequently is creeping around the inflamed segments of the small intestine. Thus, the role of several adipokines in the creeping fat as well as in intestinal inflammation was recently explored. The present review selected the four adipokines adiponectin, apelin, chemerin, and leptin and provides a working model based on the available literature how these factors participate in the maintenance of intestinal immune homeostasis.

Keywords: Crohn's disease; adipokines; creeping fat; immune modulation; inflammatory bowel disease.

Figure 1

Regulatory effect of selected adipokines on intestinal homeostasis. The figure illustrates at which layer of the intestinal wall the selected adipokines exert their respective regulatory function. Blue indicates the intestinal epithelial layer. Adiponectin, apelin and leptin have been shown to enhance cell proliferation and enhance barrier function. The majority of these data derive from in vitro data, thus it remains open how these adipokines contribute to the complex crosstalk between epithelial cells and immune cells in vivo. Green indicates the lamina propria with all cell populations included. Chemerin has been shown here to attract innate immune cells resulting in a deterioration of colitis. Leptin induces T cell proliferation thus enhancing inflammation. Yellow indicates the mesenteric fat tissue. Adiponectin, apelin and leptin are all up-regulated in this compartment. Apelin enhances the function of the lymphatic vessels, that are known to be dysfunctional in Crohn's disease. Leptin strongly influences the polarization of infiltrating monocytes toward rather anti-inflammatory macrophages.