Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats.

作者：Akira Okuno, Hiroyuki Tamemoto, Kazuuki TOBE, Kohjiro Ueki, Yusaku Mori, K Iwamoto, Kazuhiko Umesono, Y. Akanuma, Takuya Fujiwara, Hiroyoshi Horikoshi, Y Yazaki, Takashi Kadowaki · 发表于：Journal of Clinical Investigation · 年份：1998 · DOI：10.1172/jci1235 · 被引用次数：1002 · 研究领域：Peroxisome Proliferator-Activated Receptors、Adipokines, Inflammation, and Metabolic Diseases、Adipose Tissue and Metabolism

Troglitazone (CS-045) is one of the thiazolidinediones that activate the peroxisome proliferator-activated receptor gamma (PPARgamma), which is expressed primarily in adipose tissues. To elucidate the mechanism by which troglitazone relieves insulin resistance in vivo, we studied its effects on the white adipose tissues of an obese animal model (obese Zucker rat). Administration of troglitazone for 15 d normalized mild hyperglycemia and marked hyperinsulinemia in these rats. Plasma triglyceride level was decreased by troglitazone in both obese and lean rats. Troglitazone did not change the total weight of white adipose tissues but increased the number of small adipocytes (< 2,500 micron2) approximately fourfold in both retroperitoneal and subcutaneous adipose tissues of obese rats. It also decreased the number of large adipocytes (> 5,000 micron2) by approximately 50%. In fact, the percentage of apoptotic nuclei was approximately 2.5-fold higher in the troglitazone-treated retroperitoneal white adipose tissue than control. Concomitantly, troglitazone normalized the expression levels of TNF-alpha which were elevated by 2- and 1.4-fold in the retroperitoneal and mesenteric white adipose tissues of the obese rats, respectively. Troglitazone also caused a dramatic decrease in the expression levels of leptin, which were increased by 4-10-fold in the white adipose tissues of obese rats. These results suggest that the primary action of troglitazone may be to increase the number of s...