BBB seminar: Philipp Scherer
The multifaceted roles of adipose tissue: Therapeutic targets for diabetes and beyond
Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
A decrease in the plasticity of adipocytes leads to metabolic dysfunction. Furthermore, to maintain a healthy, non-inflamed phenotype in adipose tissue, complex regulatory mechanisms are in place to ensure adipocytes and stromal vascular cells efficiently crosstalk to allow adipose tissue to expand upon increased demand for storage of triglycerides. Therefore, we propose a model of stepwise adipose tissue dysfunction that is initiated by rapid expansion of existing adipocytes to accommodate triglycerides during excess caloric intake. This leads very quickly to an acute, and eventually chronic, state of hypoxia in adipose tissue. In contrast, “healthy” adipose tissue expansion has a positive effect on the systemic lipotoxic environment that usually prevails in most cases of obesity. This may be particularly relevant for sphingolipids that tend to accumulate and prompt a high level of cytotoxicity under high fat diet conditions. Adiponectin potently stimulates a ceramidase activity associated with its two receptors, adipoR1 and adipoR2, and enhances ceramide catabolism and formation of its anti-apoptotic metabolite – sphingosine-1-phosphate (S1P), independently of AMP-activated protein kinase (AMPK). These observations suggest a novel role of adipocyte-derived factors that have beneficial systemic effects, with sphingolipid metabolism as the core upstream component.
Chairperson: Nils Halberg, Department of Biomedicine