Early inflammatory responses to high saturated fat diet

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DESCRIPTION (provided by applicant): Obesity has become a major health risk in most developed countries. Recent studies in humans and animal models have shown adipose tissue to exhibit an inflammatory response to obesigenic diets that is characterized by infiltration of leukocytes and expression of inflammatory cytokines and chemokines. This response appears to contribute critically to the systemic inflammatory complications of obesity such as atherosclerosis, metabolic syndrome and steatohepatitis. Since most of the data comes from adipose tissues collected after obesity is established, there is little information available on the eady changes as a result of high saturated fat (HSF) diet. In vitro a variety of cell types are activated by treatment with saturated fatty-acids and this response is mediated through TLR4 and TLR2. Three days of HSF diet results in neutrophil infiltration of murine adipose tissues, and a single meal induces transient endotoxemia and leukocyte activation in humans. The possible roles and interaction of leukocytes resident in adipose tissue and in circulation following HSF feeding are unclear. The goal of this project is to analyze the very eady local and systemic response to HSF feeding and the cells which initiate this response. I hypothesize that leukocytes resident in the adipose tissue initiate eady changes and TLRs are necessary for their activation. To test this hypothesis I will examine molecular and cellular changes in the blood and intra- abdominal adipose tissue in a murine model of high saturated fat feeding and utilize the TLR4 deficient, TLR2-/- and leukocyte depleted mouse models to directly address my aims. There is a high association of diet and obesity with increased risk for other diseases and the number of obese persons, including children grows larger every year. It is necessary to understand the different factors that contribute to this risk, including the immediate response to a high saturated fat diet.