220 INSULIN RESISTANT INDIVIDUALS MAY BE CHARACTERIZED BY A PREPONDERANCE OF SMALLER ADIPOCYTES

Purpose There is an increasing understanding that adipose tissue not only serves as an energy storage depot but also acts as a powerful endocrine organ. Various studies have shown that important factors such as leptin, adiponectin, and resistin are not only produced in adipose tissue, but may have significant systemic effects. Such factors have been shown to be differentially expressed in insulin resistant (IR) and insulin sensitive (IS) individuals. Prior studies have suggested that adipocytes are larger in IR individuals while other studies have suggested impaired adipogenesis in IR individuals compared to IS ones. Our study aimed to test the hypothesis that there are differences in adipocyte size between IR and IS individuals and that these differences are independent of body mass index (BMI) and may be related to varying levels of differentiation. Methods Human biopsies were obtained from subcutaneous adipose tissue depots of relatively healthy overweight or obese individuals (n=10) with similar body mass index (BMI) values (IR 32.3 ± 3.8 vs. IS 29.4 ± 2.9). Insulin sensitivity was determined using steady state plasma glucose (SSPG) measurements to establish whether individuals were placed in the IR or IS group (IR 237 ± 42 vs. IS 77 ± 16 mg/dL). Adipocyte size was determined using a Multisizer Coulter Counter and were confirmed to be adipocytes by light microscopy. Gene expression levels were determined by quantitative real-time PCR. Results Although adipocyte size measurements between IR and IS groups did not differ significantly, the IR group had a higher small to large cell ratio (1.66± 1.03 vs. 0.94 ± 0.50, P ≤0.05). Adiponectin, PPARγ1, PPARγ2, and GLUT4 all showed 2-3 fold lower levels of expression in the IR group (n=5) compared to the IS group (n=5). In contrast, there were no significant differences in Adipsin and SREBP-1c expression in both groups. Conclusions Our observation of a bimodal distribution of small and large cells in both IR and IS groups, and a larger ratio of small adipocytes in IR compared to IS individuals is a novel finding. Gene expression analysis suggests that there is probably a decrease in differentiation since GLUT4 and Adiponectin, known markers of terminal adipocyte differentiation, were significantly decreased in the IR group. However since SREBP-1c and Adipsin were not differentially expressed in both groups more work will need to be done to further characterize the adipocyte differences in the IR and IS groups and to determine the significance of adipocyte size and insulin resistance status.