Abstract

Context

Circulating adiponectin levels are decreased in pregnant women with obesity or gestational diabetes, and this is believed to contribute to the insulin resistance and increased risk of fetal overgrowth associated with these conditions. However, the molecular mechanisms regulating adiponectin secretion from maternal adipose tissues in pregnancy are poorly understood.

Objective

We tested the hypothesis that obesity in pregnancy is associated with adipose tissue insulin resistance and increased adiponectin ubiquitination and degradation, caused by inflammation and endoplasmic reticulum (ER) stress.

Methods

Visceral adipose tissues were collected from lean and obese pregnant humans and mice. Total and ubiquitinated adiponectin, and markers of inflammation, ER stress, and insulin resistance were examined in adipose tissues. The role of insulin, inflammation, and ER stress in mediating adiponectin ubiquitination and degradation was examined using 3T3L-1 adipocytes.

Results

Obesity in pregnancy is associated with adipose tissue inflammation, ER stress, insulin resistance, increased adiponectin ubiquitination, and decreased total abundance of adiponectin. Adiponectin ubiquitination was increased in visceral fat of obese pregnant women as compared to lean pregnant women. We further observed that insulin prevents, whereas ER stress and inflammation promote, adiponectin ubiquitination and degradation in differentiated 3T3-L1 adipocytes.

Conclusion

We have identified adiponectin ubiquitination as a key mechanism by which obesity diminishes adiponectin secretion in pregnancy. This information will help us better understand the mechanisms controlling maternal insulin resistance and fetal growth in pregnancy and may provide a foundation for the development of strategies aimed at improving adiponectin production in pregnant women with obesity or gestational diabetes.

中文翻译：

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胰岛素通过抑制泛素化和降解增加妊娠期脂肪脂联素：肥胖的影响

摘要

语境

肥胖或妊娠糖尿病孕妇的循环脂联素水平降低，据信这会导致胰岛素抵抗和与这些疾病相关的胎儿过度生长的风险增加。然而，调节妊娠期母体脂肪组织脂联素分泌的分子机制知之甚少。

客观的

我们检验了妊娠期肥胖与脂肪组织胰岛素抵抗以及由炎症和内质网 (ER) 应激引起的脂联素泛素化和降解增加有关的假设。

方法

从瘦和肥胖的怀孕人和小鼠身上收集内脏脂肪组织。在脂肪组织中检查了总脂联素和泛素化脂联素，以及炎症、ER 应激和胰岛素抵抗的标志物。使用 3T3L-1 脂肪细胞检查了胰岛素、炎症和 ER 应激在介导脂联素泛素化和降解中的作用。

结果

妊娠期肥胖与脂肪组织炎症、内质网应激、胰岛素抵抗、脂联素泛素化增加和脂联素总丰度降低有关。与瘦孕妇相比，肥胖孕妇内脏脂肪中的脂联素泛素化增加。我们进一步观察到，胰岛素可以防止，而 ER 应激和炎症促进分化的 3T3-L1 脂肪细胞中的脂联素泛素化和降解。

结论

我们已经确定脂联素泛素化是肥胖减少妊娠期脂联素分泌的关键机制。这些信息将帮助我们更好地了解控制孕期母体胰岛素抵抗和胎儿生长的机制，并可能为制定旨在改善肥胖或妊娠糖尿病孕妇脂联素生成的策略提供基础。