Role of TLR4 in the induction of inflammatory changes in adipocytes and macrophages.

In obesity, high levels of saturated fatty acids (SFAs) contribute to adipose tissue inflammation and dysfunction. Obesity-induced macrophage infiltration leads to insulin resistance, but the adipocyte itself may play a role in generating the inflammatory milieu. Given our recent findings of the role of TLR4 in myeloid biasing in obesity, we next investigated the role of TLR4 in adipocyte generated inflammatory responses to SFAs and lipopolysaccharides. We used WT and Tlr4(-/-) ear mesenchymal stem cell derived adipocytes (EMSC Ad) and bone marrow dendritic cells (BMDCs) to evaluate cell specific responses. Our work demonstrates a role for TLR4 in adipocyte- immune cell crosstalk and that SFA derived metabolites from adipocytes may induce proinflammatory stimulation of immune cells in a TLR4 independent manner.