2008 Grant Award - Christina Koutsari, Ph.D.

Regional Free Fatty Acid Uptake Assessed by Positron Emission Tomography in Humans: A Pilot Feasibility Study

Christina Koutsari, Ph.D.
Endocrinology Research Unit, Mayo Clinic

Elevated circulating free fatty acids (FFA) are implicated in the metabolic complications of insulin resistance, obesity, and type 2 diabetes. Because of the health implications of elevated circulating FFA, body fat distribution, and ectopic fat, defining the contributions of tissues and organs to FFA clearance from the circulation can be instrumental in our understanding of FFA regulation and metabolism. There is currently limited information in humans regarding which tissues take up FFA, and what proportion of FFA disposal is allocated to different tissues (muscle, adipose, liver, heart, kidney) or different sites within heterogeneous tissues (different muscle types and adipose tissue beds). It is possible to perform tissue biopsies after the intravenous injection of an FFA tracer or measure arteriovenous balance across a tissue bed, but these approaches are not easily applicable to all tissues. Positron emission tomography (PET) imaging is a promising, non-invasive method to quantitate regional FFA uptake that is especially suited to organs that are currently inaccessible. In the present study, we will test the use of [1-11C]palmitate and PET to study FFA uptake into adipose tissue beds, skeletal muscle, and liver. We anticipate that variability will exist between different adipose tissue depots (subcutaneous versus visceral) and sites (subcutaneous abdominal versus femoral) as well as between organs. In addition, we will compare the adipose subcutaneous FFA uptake data obtained with PET to those obtained with the use of our well-established technique of [1-14C]palmitate and tissue biopsies. Successful completion of the proposed studies will allow us to examine tissue FFA uptake in conditions of differing FFA concentrations and different disease states on tissue FFA uptake. This will allow a better, more integrated understanding of the potential role of FFA in insulin resistance.