Cellularity and adipogenic profile of the abdominal subcutaneous adipose tissue from obese adolescents: association with insulin resistance and hepatic steatosis.

Cellularity and adipogenic profile of the abdominal subcutaneous adipose tissue from obese adolescents: association with insulin resistance and hepatic steatosis.
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DOI:
10.2337/db10-0113
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发表时间:
2010-09
期刊:
影响因子:
7.7
通讯作者:
Caprio S
Caprio S
中科院分区:
医学1区
文献类型:
--
作者:
Kursawe R;Eszlinger M;Narayan D;Liu T;Bazuine M;Cali AM;D'Adamo E;Shaw M;Pierpont B;Shulman GI;Cushman SW;Sherman A;Caprio S

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我们探讨了脂肪细胞大小的分布、脂肪细胞的估计总数以及皮下脂肪组织中脂肪生成基因的表达是否与肥胖青少年高内脏脂肪和低皮下脂肪储存的表型有关。共有38名肥胖程度相似的青少年同意进行皮下脐周脂肪组织活检,以及代谢(口服葡萄糖耐量试验和高胰岛素正糖钳)和成像研究(MRI, DEXA, 1H-NMR)。皮下脐周脂肪细胞的大小分布和皮下脂肪细胞的估计总数从组织活检样本固定在四氧化锇和Beckman Coulter Multisizer分析。采用Affymetrix基因芯片和定量RT-PCR检测成脂能力。受试者分为两组:高/低内脏脂肪/内脏脂肪+皮下脂肪(VAT/[VAT+SAT])。即使在调整了年龄、性别和种族后,高和低VAT/(VAT+SAT)组之间的细胞大小分布曲线也存在显著差异(方差分析P = 0.035)。令人惊讶的是,高VAT/(VAT+SAT)组大脂肪细胞的比例显著降低(P < 0.01),大脂肪细胞的估计总数也显著增加(P < 0.05),而平均直径增加(P < 0.01)。微阵列分析显示,高VAT/(VAT+SAT)组的脂肪生成/脂肪生成标志物(甾醇调节元件结合蛋白-1、乙酰辅酶a羧化酶、脂肪酸合成酶)表达较低,RT-PCR证实了这一点。脂/脂肪生成能力、脂肪含量和皮下脂肪细胞数量的减少可能导致肥胖青少年腹部脂肪和肝脏脂肪变性的异常分布,以及胰岛素抵抗。
We explored whether the distribution of adipose cell size, the estimated total number of adipose cells, and the expression of adipogenic genes in subcutaneous adipose tissue are linked to the phenotype of high visceral and low subcutaneous fat depots in obese adolescents. A total of 38 adolescents with similar degrees of obesity agreed to have a subcutaneous periumbilical adipose tissue biopsy, in addition to metabolic (oral glucose tolerance test and hyperinsulinemic euglycemic clamp) and imaging studies (MRI, DEXA, 1H-NMR). Subcutaneous periumbilical adipose cell-size distribution and the estimated total number of subcutaneous adipose cells were obtained from tissue biopsy samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. The adipogenic capacity was measured by Affymetrix GeneChip and quantitative RT-PCR. Subjects were divided into two groups: high versus low ratio of visceral to visceral + subcutaneous fat (VAT/[VAT+SAT]). The cell-size distribution curves were significantly different between the high and low VAT/(VAT+SAT) groups, even after adjusting for age, sex, and ethnicity (MANOVA P = 0.035). Surprisingly, the fraction of large adipocytes was significantly lower (P < 0.01) in the group with high VAT/(VAT+SAT), along with the estimated total number of large adipose cells (P < 0.05), while the mean diameter was increased (P < 0.01). From the microarray analyses emerged a lower expression of lipogenesis/adipogenesis markers (sterol regulatory element binding protein-1, acetyl-CoA carboxylase, fatty acid synthase) in the group with high VAT/(VAT+SAT), which was confirmed by RT-PCR. A reduced lipo-/adipogenic capacity, fraction, and estimated number of large subcutaneous adipocytes may contribute to the abnormal distribution of abdominal fat and hepatic steatosis, as well as to insulin resistance in obese adolescents.
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