Pioglitazone increases the proportion of small cells in human abdominal subcutaneous adipose tissue.
Pioglitazone increases the proportion of small cells in human abdominal subcutaneous adipose tissue.
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DOI：
10.1038/oby.2009.380
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发表时间：
2010-05
期刊：
影响因子：
6.9
通讯作者：
Sherman, A.
中科院分区：
文献类型：
--
作者：
McLaughlin, Tracey M.;Liu, T.;Yee, Gail;Abbasi, F.;Lamendola, C.;Reaven, G. M.;Tsao, P.;Cushman, S. W.;Sherman, A.
啮齿动物和体外研究表明，噻唑烷二酮类促进脂肪形成，但很少有研究在人类证实这些发现。本研究的目的是确定吡格列酮是否在体内刺激脂肪生成，以及该过程是否与改善胰岛素敏感性有关。为了检验这一假设，12名超重/肥胖非糖尿病、胰岛素抵抗个体在基线和吡格列酮治疗12周后接受腹部皮下脂肪组织活检。通过Multisizer技术测定细胞尺寸分布。通过改良的胰岛素抑制试验，在基线和吡格列酮给药后对胰岛素敏感性进行定量。通过计算机断层扫描（CT）对区域脂肪库进行定量。吡格列酮治疗后胰岛素抵抗（稳态血浆胰岛素和血糖（SSPG））降低（P < 0.001）。小细胞与大细胞的比例增加（1.16 ± 0.44 vs. 1.52 ± 0.66，P = 0.03），小细胞的绝对数量增加25%（P = 0.03）。大细胞直径的分布变宽（P = 0.009），但在小细胞的情况下，直径没有增加。小细胞比例的增加与胰岛素抵抗改善的程度相关（r =-0.72，P = 0.012）。腹部内脏脂肪减少（P = 0.04），腹部皮下脂肪（P = 0.03）和股骨脂肪（P = 0.004）显著增加。脂肪体积的变化与SSPG的变化无关。这些结果表明吡格列酮对人皮下脂肪细胞具有明确的作用，提示腹部皮下脂肪组织中的脂肪生成，以及脂肪从内脏到皮下贮库的再分布，突出了噻唑烷二酮类药物的潜在作用机制。这些发现支持了皮下脂肪储存缺陷可能是肥胖相关胰岛素抵抗的基础的假设。
Rodent and in vitro studies suggest that thiazolidinediones promote adipogenesis but there are few studies in humans to corroborate these findings. The purpose of this study was to determine whether pioglitazone stimulates adipogenesis in vivo and whether this process relates to improved insulin sensitivity. To test this hypothesis, 12 overweight/obese nondiabetic, insulin-resistant individuals underwent biopsy of abdominal subcutaneous adipose tissue at baseline and after 12 weeks of pioglitazone treatment. Cell size distribution was determined via the Multisizer technique. Insulin sensitivity was quantified at baseline and postpioglitazone by the modified insulin suppression test. Regional fat depots were quantified by computed tomography (CT). Insulin resistance (steady-state plasma insulin and glucose (SSPG)) decreased following pioglitazone (P < 0.001). There was an increase in the ratio of small-to-large cells (1.16 ± 0.44 vs. 1.52 ± 0.66, P = 0.03), as well as a 25% increase in the absolute number of small cells (P = 0.03). The distribution of large cell diameters widened (P = 0.009), but diameter did not increase in the case of small cells. The increase in proportion of small cells was associated with the degree to which insulin resistance improved (r = −0.72, P = 0.012). Visceral abdominal fat decreased (P = 0.04), and subcutaneous abdominal (P = 0.03) and femoral fat (P = 0.004) increased significantly. Changes in fat volume were not associated with SSPG change. These findings demonstrate a clear effect of pioglitazone on human subcutaneous adipose cells, suggestive of adipogenesis in abdominal subcutaneous adipose tissue, as well as redistribution of fat from visceral to subcutaneous depots, highlighting a potential mechanism of action for thiazolidinediones. These findings support the hypothesis that defects in subcutaneous fat storage may underlie obesity-associated insulin resistance.
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影响因子：
16.2
作者：
Mori, Y;Murakawa, Y;Ikeda, Y
通讯作者：
Ikeda, Y
影响因子：
8.2
作者：
Hammarstedt, A;Sopasakis, VR;Smith, U
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Smith, U
影响因子：
5.3
作者：
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Naoumova, Rossi P
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作者：
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Cha, Bong-Soo
影响因子：
7.7
作者：
GREENFIELD, MS;DOBERNE, L;REAVEN, G
通讯作者：
REAVEN, G