Start Date: Apr 01, 2009
End Date: Mar 31, 2014
The research approach to accomplish this objective employs an established animal model of diet-induced obesity, the C57BL/6J mouse strain, fed diets rich in milk fat or corn oil, compared with low-fat control diets matched for all nutrients except the level of milk fat or corn oil. At specified times of feeding, animals will be analyzed for metabolic changes induced by the diets (e.g., insulin sensitivity, RER), systemic inflammatory changes, and local inflammatory changes in intra-abdominal and subcutaneous adipose tissue depots. The inflammatory changes analyzed include gene (qPCR and/or expression arrays) and protein (ELISA and/or flow cytometry) expression of cytokines, chemokines and adhesion molecules, and leukocyte subsets phenotypically characterized (flow cytometry); and mechanistic studies will be carried out using targeted deletions of proteins potentially key to inflammatory cascades (e.g., CD11c knockouts, gamma delta T cell knockouts, TLR4 knockouts, etc., backcrossed to the C67BL/6J strain). The experimental approach analyzing anti-inflammatory factors (e.g, candidate genes such as IL-1ra or expression array analysis) influenced by changes in diet will utilize this animal model with focus on the early times following initiation of the high fat feeding and on times following reversal of the high-fat diet to a low-fat diet, a time we have found involves rapid resolution of inflammation that precede reductions in fat mass.