Differential effects of thiazolidinediones on adipocyte growth and recruitment in Zucker fatty rats

• Published in: PloS one 2009-12, Vol.4 (12), p.e8196
• Main Authors: MacKellar, Jennifer, Cushman, Samuel W, Periwal, Vipul
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - cytology; Adipocytes - drug effects; Adipose tissue; Animals; Area Under Curve; Biophysics/Theory and Simulation; Biopsy; Cell Count; Cell number; Cell Proliferation - drug effects; Cell size; Cell Size - drug effects; Cytology; Data analysis; Diabetes; Diabetes and Endocrinology/Obesity; Fatty acids; Glucose - metabolism; Glucose Tolerance Test; Hyperplasia; Hypertrophy; Insulin; Insulin resistance; Kidney diseases; Likelihood Functions; Lipids; Metabolism; Morphology; Obesity; Physiology/Morphogenesis and Cell Biology; Probability distributions; Rats; Rats, Zucker; Recruitment; Rodents; Rosiglitazone; Sensitivity; Sensitizing; Thiazolidinediones; Thiazolidinediones - pharmacology; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008196

Adipose tissue grows by two mechanisms: hyperplasia (cell number increase) and hypertrophy (cell size increase). Thiazolidinediones are insulin-sensitizing peroxisome proliferator-activated receptor gamma agonists that are known to affect the morphology of adipose tissue. In this study, adipose cell-size probability distributions were measured in six Zucker fa/fa rats over a period of 24 days, from four weeks of age, using micro-biopsies to obtain subcutaneous (inguinal) fat tissue from the animals. Three of the rats were gavaged daily with rosiglitazone, a thiazolidinedione, and three served as controls. These longitudinal probability distributions were analyzed to obtain the rate of increase in cell-size diameter in rosiglitazone-treated animals, and the hyperplasia induced by treatment quantitatively. We found that treatment leads to hypertrophy that leads to an approximately linear rate of cell diameter increase (2 m/day), and that the hyperplasia evident in treated animals occurs largely within the first eight days of treatment. The availability of additional lipid storage due to treatment may alleviate lipotoxicity and thereby promote insulin sensitivity. The hypothesis that a TZD regimen involving repeated treatments of limited duration may suffice for improvements in insulin sensitivity merits further investigation.