Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro.

Adipose dipeptidyl peptidase-4 and obesity: correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro.
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DOI:
10.2337/dc13-0496
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发表时间:
2013-12
期刊:
影响因子:
16.2
通讯作者:
Eckel J
Eckel J
中科院分区:
医学1区
文献类型:
--
作者:
Sell H;Blüher M;Klöting N;Schlich R;Willems M;Ruppe F;Knoefel WT;Dietrich A;Fielding BA;Arner P;Frayn KN;Eckel J

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研究最近发现的脂肪因子二肽基肽酶-4(DPP 4)在不同BMI和胰岛素敏感性患者的皮下脂肪组织(SAT)和内脏脂肪组织(VAT)中的表达,并评估循环DPP 4与肥胖和胰岛素敏感性的关系。DPP 4表达在SAT和VAT中测量,来自196名具有广泛BMI和胰岛素敏感性的受试者。在来自SAT和VAT的配对活检组织中离体测量DPP 4释放,以及在来自瘦和肥胖患者的SAT的体内测量DPP 4释放。在胰岛素敏感和胰岛素抵抗BMI匹配的肥胖患者中测量循环DPP 4。在SAT和VAT中,DPP 4表达与BMI呈正相关,VAT始终显示高于SAT的表达。在瘦型和肥胖患者中,从脂肪组织外植体的离体释放的DPP 4在VAT中比在SAT中更高,肥胖患者显示出比瘦型对照更高的DPP 4释放。在体内也证实了DPP 4从脂肪组织的净释放,其中肥胖受试者中的释放大于瘦受试者,女性中的释放大于男性。胰岛素敏感性肥胖患者的循环DPP 4显著低于肥胖匹配的胰岛素抵抗患者。在该实验中,DPP 4与VAT的量、脂肪细胞大小和脂肪组织炎症正相关。DPP 4是一种新型脂肪因子,从VAT中释放的量更高,这在肥胖和胰岛素抵抗患者中尤其明显。我们的数据表明,DPP 4可能是内脏肥胖,胰岛素抵抗和代谢综合征的标志物。
To study expression of the recently identified adipokine dipeptidyl peptidase-4 (DPP4) in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of patients with various BMIs and insulin sensitivities, as well as to assess circulating DPP4 in relation to obesity and insulin sensitivity. DPP4 expression was measured in SAT and VAT from 196 subjects with a wide range of BMIs and insulin sensitivities. DPP4 release was measured ex vivo in paired biopsies from SAT and VAT as well as in vivo from SAT of lean and obese patients. Circulating DPP4 was measured in insulin-sensitive and insulin-resistant BMI-matched obese patients. DPP4 expression was positively correlated with BMI in both SAT and VAT, with VAT consistently displaying higher expression than SAT. Ex vivo release of DPP4 from adipose tissue explants was higher in VAT than in SAT in both lean and obese patients, with obese patients displaying higher DPP4 release than lean controls. Net release of DPP4 from adipose tissue was also demonstrated in vivo with greater release in obese subjects than in lean subjects and in women than in men. Insulin-sensitive obese patients had significantly lower circulating DPP4 than did obesity-matched insulin-resistant patients. In this experiment, DPP4 positively correlated with the amount of VAT, adipocyte size, and adipose tissue inflammation. DPP4, a novel adipokine, has a higher release from VAT that is particularly pronounced in obese and insulin-resistant patients. Our data suggest that DPP4 may be a marker for visceral obesity, insulin resistance, and the metabolic syndrome.