Comparison of adipose tissue changes following administration of rosiglitazone in the dog and rat

Rosiglitazone (BRL-49653-C), a thiazolidinedione, is a potent agonist for t he nuclear hormone receptor peroxisome proliferator-activated receptor gamm a (PPARg). Thiazolidinediones have been reported to induce adipocyte differ entiation in vitro and there is limited data on their effects in vivo. The objective of this study was to compare the effects of rosiglitazone on adip ocyte differentiation between dogs and rats. Morphological (light and ultra structural) and morphometric evaluations were conducted on perirenal adipos e tissue from dogs that have been treated for 1 month with 0.4, 5, 60 mg/kg /day and rats treated for the same period with 80 mg/kg/day. There was a do se-related change in the phenotype of white adipose tissue in dogs, reflect ed by an increase in nuclear numerical density (up to threefold) and cytopl asmic area fraction (up to 2.1-fold). In addition, there was an enlargement of the nuclei and a reduction in the size of the white adipocyte lipid vac uoles. Ultrastructural changes included an increase in the number of mitoch ondria per adipocyte. In the rat, similar changes were seen in nuclear nume rical density (1.5-fold increase) and cytoplasmic area fraction (2.2-fold i ncrease). There were also increased numbers of mitochondria per cell in whi te adipocytes giving them similar numbers of mitochondria to brown adipocyt es, In the brown adipocytes, there was a reduction in cytoplasmic area frac tion with a corresponding increase in the size of the lipid filled vacuoles in other words there was a converging of the phenotypes of the white and b rown adipose tissues.