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. Sub-project 5 description BACKGROUND. Obesity is a significant risk factor for many diseases, including diabetes and atherosclerosis. Obese individuals often are in a state of chronic inflammation, with elevated plasma levels of cytokines and acute phase proteins, which hampers insulin signaling. Their adipose tissues, especially near the intestine (""""""""visceral fat""""""""), also are often inflamed and infiltrated with lymphocytes and macrophages. The reason for this is unknown. Our hypothesis is that high-fat diets, a common risk factor in obesity, cause (1) intestinal absorption of inflammatory microbial antigens into visceral adipose tissue and (2) a general breakdown of immunological tolerance to gut antigens, and thus chronic inflammatory responses to the microflora. DESIGN. Using mouse models, we measure intestinal absorption of antigens from the gut in relation to fat intake as well as subsequent antigen content of visceral adipose tissue. We also measure the effect of high fat diets on the intestinal mucosal immune system (predominantly dendritic cells) and on systemic antibody responses against the microflora, to determine whether excess fat intake prevents our body to contain the microflora in a non-inflammatory manner. Lastly, we are currently identifying gut bacterial species against which IgG is being formed during diet-induced obesity, in the hope to identify those species that promote inflammation during diet-induced obesity.

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National Center for Research Resources (NCRR)
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University of Kentucky
Internal Medicine/Medicine
Schools of Medicine
United States
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