Maternal melatonin programs the daily pattern of energy metabolism in adult offspring.

Maternal melatonin programs the daily pattern of energy metabolism in adult offspring.
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孕产妇褪黑激素对成人后代的能量代谢的日常模式编写。

DOI:
10.1371/journal.pone.0038795
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Anhê GF
Anhê GF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ferreira DS;Amaral FG;Mesquita CC;Barbosa AP;Lellis-Santos C;Turati AO;Santos LR;Sollon CS;Gomes PR;Faria JA;Cipolla-Neto J;Bordin S;Anhê GF

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最近,轮班工作被描述为增加 2 型糖尿病风险的一个因素。此外,在整个怀孕期间经历相移的母亲所生的老鼠是葡萄糖不耐受的。然而,相移将代谢信息传递给后代的机制尚未确定。在几种内分泌分泌物中,光/暗周期的相移被描述为改变松果体产生褪黑激素的昼夜节律特征。本研究探讨了母体褪黑激素对于后代代谢编程的重要性。雌性 Wistar 大鼠接受 SHAM 手术或松果体切除术 (PINX)。 PINX 大鼠被分为两组,并接受褪黑激素 (PM) 或载体。 SHAM、PINX 载体和雌性 PM 与雄性 Wistar 大鼠一起饲养。让大鼠交配,断奶后,对雄性和雌性后代进行葡萄糖耐量试验(GTT)、丙酮酸耐量试验(PTT)和胰岛素耐量试验(ITT)。分离胰岛进行胰岛素分泌,并通过蛋白质印迹评估肝脏和骨骼肌中的胰岛素信号传导。我们发现,PINX 母亲所生的雄性和雌性大鼠在光/暗周期的光期结束时表现出葡萄糖不耐受,但在开始时则不然。我们进一步证明,葡萄糖刺激的胰岛素分泌受损和肝脏胰岛素抵抗可能是导致 PINX 母亲后代葡萄糖不耐受的机制。这里描述的代谢编程是由于母体褪黑激素的缺乏而发生的,因为接受褪黑激素治疗的 PINX 母亲所生的后代没有葡萄糖不耐症。目前的结果支持了这样一个新概念:母体褪黑激素负责其后代每日能量代谢模式的编程。
Shift work was recently described as a factor that increases the risk of Type 2 diabetes mellitus. In addition, rats born to mothers subjected to a phase shift throughout pregnancy are glucose intolerant. However, the mechanism by which a phase shift transmits metabolic information to the offspring has not been determined. Among several endocrine secretions, phase shifts in the light/dark cycle were described as altering the circadian profile of melatonin production by the pineal gland. The present study addresses the importance of maternal melatonin for the metabolic programming of the offspring. Female Wistar rats were submitted to SHAM surgery or pinealectomy (PINX). The PINX rats were divided into two groups and received either melatonin (PM) or vehicle. The SHAM, the PINX vehicle and the PM females were housed with male Wistar rats. Rats were allowed to mate and after weaning, the male and female offspring were subjected to a glucose tolerance test (GTT), a pyruvate tolerance test (PTT) and an insulin tolerance test (ITT). Pancreatic islets were isolated for insulin secretion, and insulin signaling was assessed in the liver and in the skeletal muscle by western blots. We found that male and female rats born to PINX mothers display glucose intolerance at the end of the light phase of the light/dark cycle, but not at the beginning. We further demonstrate that impaired glucose-stimulated insulin secretion and hepatic insulin resistance are mechanisms that may contribute to glucose intolerance in the offspring of PINX mothers. The metabolic programming described here occurs due to an absence of maternal melatonin because the offspring born to PINX mothers treated with melatonin were not glucose intolerant. The present results support the novel concept that maternal melatonin is responsible for the programming of the daily pattern of energy metabolism in their offspring.
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