Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats
Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats
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DOI：
10.1172/jci1235
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发表时间：
1998-03-15
影响因子：
15.9
通讯作者：
Kadowaki, T
中科院分区：
文献类型：
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作者：
Okuno, A;Tamemoto, H;Kadowaki, T
曲格列酮（CS-045）是噻唑烷二酮类药物之一，可激活过氧化物酶体增殖物激活受体γ（PPARγ），主要在脂肪组织中表达。为了阐明曲格列酮减轻体内胰岛素抵抗的机制，我们研究了其对肥胖动物模型（肥胖）白色脂肪组织的影响。 Zucker大鼠），给予曲格列酮15天使这些大鼠的轻度高血糖正常化，并显着高胰岛素血症。曲格列酮可降低肥胖和瘦大鼠的血浆甘油三酯水平，曲格列酮不改变白色脂肪组织的总重量，但使肥胖大鼠腹膜后和皮下脂肪组织中小脂肪细胞（<2,500μm(2)）的数量增加约四倍，还减少大脂肪细胞（> 5,000 μ m(2)) 大约 50%。事实上，在曲格列酮处理的腹膜后白色脂肪组织中，凋亡细胞核的百分比比对照高2.5倍。同时，曲格列酮使肥胖大鼠腹膜后和肠系膜白色脂肪组织中的TNF-α表达水平正常化，分别升高2倍和1.4倍， 曲格列酮还导致瘦素表达水平急剧下降，在肥胖大鼠的白色脂肪组织中瘦素表达水平增加了 4-10 倍。这些结果表明曲格列酮的主要作用可能是通过 PPAR γ 增加白色脂肪组织中小脂肪细胞的数量。曲格列酮治疗的肥胖大鼠白色脂肪组织中小脂肪细胞数量的增加和大脂肪细胞数量的减少似乎是TNF-α表达水平增加和血浆脂质水平升高正常化的重要机制，从而减轻胰岛素抵抗。
Troglitazone (CS-045) is one of the thiazolidinediones that activate the peroxisome proliferator-activated receptor gamma (PPAR gamma), 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 mu m(2)) approximately fourfold in both retroperitoneal and subcutaneous adipose tissues of obese rats, It also decreased the number of large adipocytes (> 5,000 mu m(2)) by similar to 50%. In fact, the percentage of apoptotic nuclei was similar to 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 small adipocytes in white adipose tissues, presumably via PPAR gamma. The increased number of small adipocytes and the decreased number of large adipocytes in white adipose tissues of troglitazone-treated obese rats appear to be an important mechanism by which increased expression levels of TNF-alpha and higher levels of plasma lipids are normalized, leading to alleviation of insulin resistance.