Hellenic National Center for the Research, Prevention and Treatment of Diabetes Mellitus and its Complications (H.N.D.C), Ploutarchou 3, 10675 Athens, Greece.
2nd Department of Internal Medicine, Research Institute and Diabetes Center, National and Kapodistrian University of Athens, Medical School, University General Hospital Attikon, Rimini 1, 12462 Haidari, Athens, Greece.
Peptides. 2018 Mar;101:157-166. doi: 10.1016/j.peptides.2018.01.005. Epub 2018 Jan 11.
Maternal adipose tissue and the placenta secrete various molecules commonly called adipokines such as chemerin, omentin-1, visfatin, adiponectin, and leptin that are important players in the pathogenesis of insulin resistance. Gestational diabetes mellitus (GDM) is defined as a state of glucose intolerance characterized by β-cell dysfunction and insulin resistance. To examine whether circulating adipokines and their mRNA expression in the adipose tissue and the placenta are altered in GDM pregnancy, we compared 15 GDM women [obese (BMI > 30) and non-obese (BMI < 30)] to 23 NGT (normal glucose tolerance) women [obese and non-obese], at the time of the Cesarean section. Circulating chemerin and leptin were higher (p = 0.009 and p = 0.005, respectively) and circulating omentin-1, visfatin, as well as the adiponectin/leptin ratio were lower (p = 0.039, p = 0.007 and p = 0.011, respectively) in GDM-obese compared to NGT-non-obese women. Chemerin and leptin correlated positively with BMI and HOMA-IR and omentin-1 correlated negatively with BMI. Serum TNF-α was significantly elevated in all obese compared to non-obese pregnant women and correlated positively with BMI. Adiponectin levels were reduced -although not significantly- in GDM- and NGT-obese women compared to their non-obese counterparts. Resistin, RPB4 and IL-6 levels did not differ significantly between groups. Chemerin mRNA expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was significantly higher compared to placenta in all women (6-to 24-times, p < 0.05). Chemerin-VAT mRNA expression in GDM-obese tended to be significantly higher compared to NGT-non-obese women (3-times, p = 0.005). Omentin-1 mRNA expression was significantly higher in VAT compared to SAT (50- to 100-times, p < 0.01) and its expression in placenta was negligible in all women. Although, leptin was expressed significantly higher in SAT compared to VAT and the placenta in all women (5- to 46-times, p < 0.05), only its mRNA expression in VAT of obese (GDM and NGT) differed significantly when compared to NGT-non-obese women (3-times higher, p < 0.02). Visfatin mRNA expression was comparable in all tissues. In conclusion, chemerin and leptin are elevated and omentin-1 and visfatin levels are decreased in GDM women complicated by obesity. This finding together with the positive association of chemerin and leptin with markers of insulin resistance, suggests that these adipokines and more especially chemerin and leptin accompanied by their adipose tissue expression could contribute to the increased insulin resistance and low grade inflammation that characterizes GDM-obese women.
母体脂肪组织和胎盘分泌各种分子,通常称为脂肪因子,如趋化素、网膜素-1、内脂素、脂联素和瘦素,它们是胰岛素抵抗发病机制中的重要参与者。妊娠期糖尿病(GDM)被定义为一种葡萄糖耐量异常的状态,其特征为β细胞功能障碍和胰岛素抵抗。为了研究 GDM 妊娠中循环脂肪因子及其在脂肪组织和胎盘中的 mRNA 表达是否发生改变,我们比较了 15 名 GDM 妇女(肥胖[BMI > 30]和非肥胖[BMI < 30])与 23 名 NGT(正常葡萄糖耐量)妇女(肥胖和非肥胖),在剖宫产时。循环趋化素和瘦素水平升高(p = 0.009 和 p = 0.005),循环网膜素-1、内脂素以及脂联素/瘦素比值降低(p = 0.039、p = 0.007 和 p = 0.011),GDM 肥胖组与 NGT 非肥胖组相比。趋化素和瘦素与 BMI 和 HOMA-IR 呈正相关,而网膜素-1与 BMI 呈负相关。所有肥胖的孕妇与非肥胖的孕妇相比,血清 TNF-α 显著升高,且与 BMI 呈正相关。脂联素水平在 GDM 和 NGT 肥胖组妇女中均显著降低(尽管无统计学意义),与非肥胖组相比。抵抗素、RPB4 和 IL-6 水平在各组之间无显著差异。在所有女性中,脂肪组织(SAT)和内脏脂肪组织(VAT)中的趋化素 mRNA 表达均明显高于胎盘(6-24 倍,p < 0.05)。与 NGT 非肥胖组相比,GDM 肥胖组中趋化素-VAT mRNA 表达趋于显著升高(3 倍,p = 0.005)。网膜素-1 在 VAT 中的表达明显高于 SAT(50-100 倍,p < 0.01),且在所有女性的胎盘中表达可忽略不计。尽管瘦素在 SAT 中的表达明显高于 VAT 和胎盘(5-46 倍,p < 0.05),但只有 VAT 中的瘦素 mRNA 表达在 GDM 和 NGT 肥胖组与 NGT 非肥胖组之间存在显著差异(高 3 倍,p < 0.02)。内脂素 mRNA 表达在所有组织中相似。总之,在肥胖的 GDM 妇女中,趋化素和瘦素升高,而网膜素-1 和内脂素水平降低。这一发现以及趋化素和瘦素与胰岛素抵抗标志物的正相关,表明这些脂肪因子,尤其是趋化素和瘦素,以及它们的脂肪组织表达,可能导致 GDM 肥胖妇女胰岛素抵抗和低度炎症增加。