L. Ashley Cowart
Medical University of South Carolina, USA
Title: Sphingosine-1-Phosphate signaling regulates key metabolic outcomes of obesity
Biography
Biography: L. Ashley Cowart
Abstract
Sphingosine-1-phosphate is a lysophospholipid signaling molecule that works through both receptor dependent and independent mechanisms. Sphingosine-1-phosphate is generated via phosphorylation of sphingosine by Sphingosine Kinases. We discovered that Sphingosine Kinase 1 is upregulated by saturated fatty acids, a finding which placed this pathway in the context of metabolic homeostasis. Since those initial studies, our group and others have demonstrated roles for Sphingosine Kinase 1 in pathophysiological processes in numerous organs including pancreas, skeletal muscle, adipose tissue, and liver. Moreover, ablation of this pathway in mice conferred resistance to obesity-induced inflammation and insulin resistance. Together, these data have supported the general idea that Sphingosine Kinase 1 mediates obesity-induced disease. To gain more mechanistic insights, we recently generated mice with an adipocyte-specific sphingosine kinase 1 deletion. Data from these animals has revealed novel and surprising roles for this pathway in maintaining metabolic homeostasis. For example, in contrast to the whole-body deletion, which exhibits protection from obesity-induced insulin resistance, the adipocyte-specific sphingosine kinase 1 deletion mouse exhibits basal insulin resistance. These and other data have revealed that this pathway serves both protective and deleterious roles depending on cell type and disease context. Ongoing work in the laboratory is addressing the specific roles for sphingosine-1-phosphate signaling in regulating crucial adipocyte functions including lipogenesis, lipolysis, proliferation, and differentiation. These pathways might eventually be pharmacologically targeted for treatment of obesity and/or obesity-induced disease.