This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Patients with inflammatory bowel disease, such as Crohn's and ulcerative colitis (UC), are at increased risk for developing colorectal cancer. In addition, obesity, an established risk factor for colorectal cancer, is characterized by the accumulation of excessive adipose tissue, which is the source of a variety of biologically active substances, collectively referred to as adipokines. It has been shown that adiponectin (APN), an adipokine decreased in obesity, is found in low levels in colorectal cancer patients. Preliminary data have shown that APN knock out (KO) mice were prone to develop more colon tumors than C57Bl/6 mice when received a carcinogen 1,2-dimethylhydrazine (DMH). The adenomatous polyposis coli multiple intestinal neoplasia (ApcMin/+) mouse model presents phenotypes reminiscent of Familial Adenomatous Polyposis (FAP) in humans which lead to the development of adenocarcinomas. In addition to the first animal model and in order to determine the role of APN in tumor development in ApcMin/+, we generated ApcMin/+APN KO mice and found that these mice developed more and larger tumors and have more intestinal inflammation than ApcMin/+ alone.
The specific aims of this study are: 1) to determine the effect of APN deficiency on colon tumor development in APNKO treated with DSS+DMH;2) to determine the effect of APN deficiency on colon tumor development in APCMin/+ mice;3) to determine the effect of high fat diet (obesity, the physiological condition of low APN level) on ApcMin/+APN KO colon tumor development. In all aims, we will administer APN systemically and study its effect on colon tumor growth.
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