Disruption of O-Linked N-Acetylglucosamine Signaling in Placenta Induces Insulin Sensitivity in Female Offspring.
Disruption of O-Linked N-Acetylglucosamine Signaling in Placenta Induces Insulin Sensitivity in Female Offspring.
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DOI：
10.3390/ijms22136918
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发表时间：
2021-06-28
影响因子：
5.6
通讯作者：
Alejandro EU
中科院分区：
文献类型：
--
作者：
Moore M;Avula N;Jo S;Beetch M;Alejandro EU
胎盘功能障碍可导致胎儿生长受限，这与围产期发病率和死亡率相关。胎儿生长受限会增加日后患肥胖症和糖尿病的风险。在产前应激的情况下，胎盘O - GlcNAc转移酶（OGT）已被确定为胎盘功能不全的标志物和介质，然而，它在胎儿代谢编程和葡萄糖稳态中的作用仍然未知。我们的目的是确定胎盘OGT减少的后代的长期代谢结果。利用Cre - Lox系统培育出胎盘特异性OGT部分减少和完全敲除的小鼠。在正常饮食和高脂肪饮食条件下，对成年雄性和雌性后代的葡萄糖稳态和代谢参数进行了评估。与标准饮食的对照组相比，胎盘OGT减少在代谢参数或葡萄糖稳态方面未显示出差异。高脂肪饮食带来了代谢挑战，结果显示胎盘OGT部分减少的后代体重增加减少（p = 0.02），胰岛素耐受性提高（p = 0.03），但OGT完全敲除时则没有这种情况。体重变化与能量稳态变化无关。胎盘OGT部分减少的后代在胰岛素治疗时肝脏Akt磷酸化增加（p = 0.02）。当面临高脂肪饮食的代谢挑战时，胎盘OGT部分减少对体重增加和胰岛素不耐受具有保护作用。这似乎部分是由于肝脏胰岛素信号增强。这项研究的结果有助于更好地理解胎儿代谢编程以及胎盘OGT对外周胰岛素敏感性的影响，并为未来的研究和临床应用提供了一个目标。
Placental dysfunction can lead to fetal growth restriction which is associated with perinatal morbidity and mortality. Fetal growth restriction increases the risk of obesity and diabetes later in life. Placental O-GlcNAc transferase (OGT) has been identified as a marker and a mediator of placental insufficiency in the setting of prenatal stress, however, its role in the fetal programming of metabolism and glucose homeostasis remains unknown. We aim to determine the long-term metabolic outcomes of offspring with a reduction in placental OGT. Mice with a partial reduction and a full knockout of placenta-specific OGT were generated utilizing the Cre-Lox system. Glucose homeostasis and metabolic parameters were assessed on a normal chow and a high-fat diet in both male and female adult offspring. A reduction in placental OGT did not demonstrate differences in the metabolic parameters or glucose homeostasis compared to the controls on a standard chow. The high-fat diet provided a metabolic challenge that revealed a decrease in body weight gain (p = 0.02) and an improved insulin tolerance (p = 0.03) for offspring with a partially reduced placental OGT but not when OGT was fully knocked out. Changes in body weight were not associated with changes in energy homeostasis. Offspring with a partial reduction in placental OGT demonstrated increased hepatic Akt phosphorylation in response to insulin treatment (p = 0.02). A partial reduction in placental OGT was protective from weight gain and insulin intolerance when faced with the metabolic challenge of a high-fat diet. This appears to be, in part, due to increased hepatic insulin signaling. The findings of this study contribute to the greater understanding of fetal metabolic programming and the effect of placental OGT on peripheral insulin sensitivity and provides a target for future investigation and clinical applications.
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影响因子：
5
作者：
Carvalho, Diego Soares;Diniz, Marilia Melo;Hirata, Aparecida Emiko
通讯作者：
Hirata, Aparecida Emiko
影响因子：
3.8
作者：
Jansson, T.;Aye, I. L. M. H.;Goberdhan, D. C. I.
通讯作者：
Goberdhan, D. C. I.
影响因子：
5.8
作者：
Hofman, PL;Cutfield, WS;Gluckman, PD
通讯作者：
Gluckman, PD
DOI：
10.1111/j.1749-6632.2010.05798.x
发表时间：
2010-01-01
期刊：
YEAR IN DIABETES AND OBESITY
影响因子：
--
作者：
Fernandez-Twinn, Denise S.;Ozanne, Susan E.
通讯作者：
Ozanne, Susan E.
影响因子：
10.6
作者：
Alejandro, Emilyn U.;Gregg, Brigid;Blandino-Rosano, Manuel;Cras-Meneur, Corentin;Bernal-Mizrachi, Ernesto
通讯作者：
Bernal-Mizrachi, Ernesto