Hypoxia causes reductions in birth weight by altering maternal glucose and lipid metabolism.
Hypoxia causes reductions in birth weight by altering maternal glucose and lipid metabolism.
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DOI：
10.1038/s41598-018-31908-2
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发表时间：
2018-09-11
影响因子：
4.6
通讯作者：
Koivunen P
中科院分区：
文献类型：
--
作者：
Määttä J;Sissala N;Dimova EY;Serpi R;Moore LG;Koivunen P
高海拔（>2500 m）缺氧使新生儿出生体重下降。较低的出生体重与婴儿死亡率和发病率有关，并增加了日后患心血管和代谢疾病的易感性。我们试图确定缺氧对母体葡萄糖和脂质代谢的影响及其对胎儿体重的影响。在妊娠中期（E9.5）或妊娠晚期（E17.5）研究了整个妊娠期间饲养在常压缺氧（15%氧气）或常氧环境中的C57 BL 6/NCr 1小鼠。E17.5时，缺氧条件下的胎儿体重比常氧条件下低7%。与常氧母鼠相比，缺氧母鼠在妊娠中期和晚期的性腺白色脂肪组织减少约20%。缺氧母鼠比常氧母鼠有更好的葡萄糖耐量和胰岛素敏感性，并且在妊娠后期没有出现胰岛素抵抗。他们的胰高血糖素水平也有所增加。低氧母鼠对大多数母体组织的葡萄糖摄取量是常氧母鼠的2倍。缺氧时母体代谢的改变与缺氧诱导因子（HIF）靶基因的上调有关，HIF靶基因反过来又增加糖酵解代谢。我们的结论是，环境缺氧通过上调HIF-通路改变母体代谢，并建议在高海拔妊娠中拮抗这种代谢变化的干预措施可能有助于保护胎儿生长。
Hypoxia of residence at high altitude (>2500 m) decreases birth weight. Lower birth weight associates with infant mortality and morbidity and increased susceptibility to later-in-life cardiovascular and metabolic diseases. We sought to determine the effects of hypoxia on maternal glucose and lipid metabolism and their contributions to fetal weight. C57BL6/NCrl mice, housed throughout gestation in normobaric hypoxia (15% oxygen) or normoxia, were studied at mid (E9.5) or late gestation (E17.5). Fetal weight at E17.5 was 7% lower under hypoxia than normoxia. The hypoxic compared with normoxic dams had ~20% less gonadal white adipose tissue at mid and late gestation. The hypoxic dams had better glucose tolerance and insulin sensitivity compared with normoxic dams and failed to develop insulin resistance in late gestation. They also had increased glucagon levels. Glucose uptake to most maternal tissues was ~2-fold greater in the hypoxic than normoxic dams. The alterations in maternal metabolism in hypoxia were associated with upregulation of hypoxia-inducible factor (HIF) target genes that serve, in turn, to increase glycolytic metabolism. We conclude that environmental hypoxia alters maternal metabolism by upregulating the HIF-pathway, and suggest that interventions that antagonize such changes in metabolism in high-altitude pregnancy may be helpful for preserving fetal growth.
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影响因子：
3.6
作者：
Soria, Rudy;Julian, Colleen G.;Giussani, Dino A.
通讯作者：
Giussani, Dino A.
DOI：
10.1073/pnas.1002443107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Beall, Cynthia M.;Cavalleri, Gianpiero L.;Zheng, Yong Tang
通讯作者：
Zheng, Yong Tang
DOI：
10.1161/atvbaha.115.307136
发表时间：
2016-04-01
影响因子：
8.7
作者：
Rahtu-Korpela, Lea;Maatta, Jenni;Koivunen, Peppi
通讯作者：
Koivunen, Peppi
影响因子：
4.5
作者：
Bigham A;Bauchet M;Pinto D;Mao X;Akey JM;Mei R;Scherer SW;Julian CG;Wilson MJ;López Herráez D;Brutsaert T;Parra EJ;Moore LG;Shriver MD
通讯作者：
Shriver MD
影响因子：
4.7
作者：
Karsikas, Sara;Myllymaki, Mikko;Koivunen, Peppi
通讯作者：
Koivunen, Peppi