The effect of Rosiglitazone, an insulin sensitizing drug, on adipogenesis and adipocyte size

Thiazolidinediones (TZD), or glitazones, represent a new generation of antidiabetic drugs that have been shown to improve insulin resistance, one of the key anomalies involved in the pathogenesis of type 2 diabetes mellitus, by activating the nuclear peroxoxisome proliferator activated receptor-gamma (PPAR-gamma), leading to crucial metabolic alterations in adipose tissue. Though the exact mechanism that leads to the improvement of insulin sensitivity is unclear, it has been postulated that the effect could be due to TZD’s modulation on the number and/or the size of adipocytes. To investigate, male C57/BL6 mice were treated with rosiglitazone for 4, 8, 12, 20, and 40 days after 8 weeks of high fat diet to induce insulin resistance. For cell number, 2H2O labeling was utilized to measure adipocyte DNA synthesis as a measurement for adipocyte proliferation. Adipocyte size was measured by calculating the sectional area of adipocytes after the adipose tissue was fixed with osmium tetraoxide, sliced to 5 μm thickness, and visualized under light microscope. Insulin sensitivity was assessed by the oral glucose tolerance test (OGTT). As seen previously, insulin sensitivity was significantly improved, but only after 40 days on Rosiglitazone. The treatment did not affect the adipocyte proliferation in both epididymal and inguinal fat pads, as the differences between control and treatment groups were insignificant. Preliminary result showed decreased epididymal adipocyte size and increased inguinal adipocyte size, suggesting beneficial fat redistribution from visceral fat pads to subcutaneously fat pads. In conclusion, rosiglitazone’s effect on improving insulin sensitivity is likely through modulating adipocyte size at different adipose tissue sites.