This pilot study addresses the relationship between insulin resistance and body fat distribution from the perspective of nutrient partitioning caused by differences in insulin action in muscle and adipose tissue. Our hypothesis is based on the fact that insulin resistance is initially expressed in skeletal muscle but not in adipose tissue and that some obese individuals remain insulin resistant. Recent evidence in 12 obese females indicates that of several measures of body fat distribution determined by MRI, the subcutaneous abdominal:femoral fat ratio correlated best with changes in insulin resistance after weight loss. This ratio was significantly reduced in patients whose insulin action following significant weight reduction. On the other hand, intra-abdominal fat was not significantly correlated with changes in insulin action. We plan to show that insulin resistance generates a nutrient partition gradient which favors fat deposition in the subcutaneous abdominal area. The gradient will be defined by simultaneous measurement of insulin actions on glucose uptake and antilipolysis in a group of 15 obese insulin- resistant women and 15 healthy controls. Antilipolysis will be measured in the whole body (isotope dilution), in the abdominal subcutaneous compartment by microdialysis probes (in vivo), and in fat cells by tissue biopsy (in vitro). Total body fat and distribution will be measured. This pilot investigation will provide background for more definitive studies on the relationship between insulin resistance and body composition.
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