Lay Summary

Proposal No.  IBD-0168R
Principal Investigator:  Razvan I. Arsenescu, M.D.
Applicant Organization:  University of Kentucky Research Foundation, Inc. (Lexington, U.S.A.)
Project Title:  Adiponectin in Crohn's disease.  Phenotype-genotype correlations and implications in management. 
Period of Award:  December 1, 2005 - November 30, 2008

Adiponectin is a hormone secreted exclusively by fat tissue cells that helps burn fat and improves the body’s ability to utilize sugar.  It also helps the immune system and can dampen the effects of the strong pro-inflammatory molecule called tumor necrosis factor alpha (TNFα).  Adiponectin can circulate in the blood either as single molecule (monomer) or as a complex of many adiponectin molecules (multimer).  The multimers are more potent then monomers.  Patients with diabetes, atherosclerosis, and fatty liver all seem to have lower blood levels of adiponectin and/or less of the adiponectin as multimers.

Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract that is thought to result from inappropriate and ongoing activation of the gut’s immune system, driven by the presence of normal bacteria that live here.  Inappropriate activation of the immune system is associated with too much TNFα.  Reducing the amounts of TNFα in Crohn’s patients has become the most recent successful and exciting therapy for them.

We propose that decreased level of adiponectin and/or decreased level of the multimeric form contribute to the chronic inflammation seen in Crohn’s disease patients.

This theory suggests that less adiponectin allows TNFα to generate too much inflammation. To test our hypothesis, we will evaluate Crohn’s disease patients and normal individuals and measure their adiponectin levels, the amounts of multimers and assess the adiponectin gene mutations.  We will then correlate changes in adiponectin gene and protein with Crohn’s disease activity, the types of complications seen and how patients responded to standard treatments.

Identifying patients with low levels of adiponectin or less adiponectin as multimers will justify future experiments in which we give adiponectin to Crohn’s patients as a possible therapy to regulate the inflammation.  In addition, we will be able to customize treatment, therefore maximizing benefits and decreasing side-effects.