Role of MCH in Adipose Tissue & Intestinal Inflammation

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DESCRIPTION (provided by applicant): Melanin-concentrating hormone (MCH), a hypothalamic neuropeptide that regulates appetite and body weight, has also been shown to play a proinflammatory role in colitis of various etiologies. Thus, mesenteric human preadipocytes express MCH receptors, and MCH binding to these receptors stimulates expression of IL-8, a neutrophil chemoattractant involved in IBD pathogenesis. Since patients with Crohn's disease have mesenteric fat wrapping of the bowel associated with increased expression of proinflammatory cytokines, it is likely that MCH participates in this inflammatory response. The goals of this study are two-fold: 1) To examine the hypothesis that MCH links mucosal inflammation with inflammatory changes in the mesenteric fat depots during colitis and 2) that NF-kB and MAP kinase pathways contribute to the signaling involved. This will be done by comparing MCH and MCH-receptor expression at the protein and mRNA levels in murine fat depots to degree of mucosal inflammation during TNBS-, DSS-, and IL-10 KO colitis, identifying the cells expressing MCH/MCHR1 in this tissue through laser capture microdissection, immunohistochemical analysis, and confocal microscopy and dissecting signalling pathways by western blot, RT-PCR and ELISA.