Influence of Free Fatty Acid Concentrations and Weight Loss on Adipose Tissue Direct Free Fatty Acid Storage Rates

Context: The factors that determine the recycling of free fatty acids (FFA) back into different adipose tissue depots via the direct storage pathway are not completely understood. Objective: To assess the interactions between adipocyte factors and plasma FFA concentrations that determine regional FFA storage rates. Design: We measured direct adipose tissue FFA storage rates before and after weight loss under high FFA (intravenous somatostatin and epinephrine) and low (intravenous insulin and glucose) FFA concentrations. Setting: Mayo Clinic Clinical Research Unit. Patients: Sixteen premenopausal women, body mass index 30 to 37 kg/m2. Intervention: Comprehensive lifestyle weight loss program. Main Outcome Measure: Direct FFA storage rates in upper and lower body subcutaneous fat. Results: Over the entire range of FFA and under isolated conditions of elevated FFA concentrations, the storage rates of FFA into upper and lower body subcutaneous fat per unit lipid were associated with concentrations, not adipocyte fatty acid storage factors. Under low FFA conditions, direct FFA storage rates were related to adipocyte CD36 content, not tissue level content of fatty acid storage factors. Weight loss did not change these relationships. Conclusions: The regulation of direct FFA storage under low FFA concentration conditions appears to be at the level of the cell/adipocyte content of CD36, whereas under high FFA concentration conditions, direct FFA storage at the tissue level is predicted by plasma FFA concentrations, independent of adipocyte size or fatty acid storage factors. These observations offer novel insights into how adipose tissue regulates direct FFA storage in humans.