Metabolic syndrome is a cluster disorder characterized comorbid health conditions, such as increased fat around waist, increased circulating triglyceride and cholesterol levels, and hyperglycemia. Together, these disorders increase an individual’s risk of cardiovascular disease, Type II diabetes, and stroke. In the U.S., nearly 25 percent of the adult population has been diagnosed with metabolic syndrome making it increasingly common. Interestingly, the group of disorders underlying metabolic syndrome are often associated with chronic inflammation. iNKT cells have been reported to regulate macrophage polarization within the adipose tissue. Despite our understanding of iNKT cell-macrophage interactions in disease pathogenesis, the specific mechanisms that underly pro-inflammatory polarization of these interactions in the context of chronic inflammation remain unclear. Herein, this study seeks to address the role of the lipid metabolism regulator, SREBP1, in facilitating iNKT cell-macrophage interactions and pro-inflammatory polarization in the context of chronic inflammation. We hypothesize that during chronic inflammation decreases in SREBP1 expression in macrophages increases CD1d-mediated iNKT activation. We will test our hypothesis using both SREBP1 inhibitors and genetic ablation of SREBP1 in the presence or absence of inflammatory agents in vitro and in vivo models. This work will aid in understanding the mechanisms by which the interplay between iNKT cells and macrophage in the context of chronic inflammation dictate outcomes in metabolic disorders.
Â