Abstract:
OBJECTIVE:During pregnancy, women normally increase their food intake and body fat mass, and exhibit insulin resistance. However, an increasing number of women are developing metabolic imbalances during pregnancy, including excessive gestational weight gain and gestational diabetes mellitus. Despite the negative health impacts of pregnancy-induced metabolic imbalances, their molecular causes remain unclear. Therefore, the present study investigated the molecular mechanisms responsible for orchestrating the metabolic changes observed during pregnancy. METHODS:Initially, we investigated the hypothalamic expression of key genes that could influence the energy balance and glucose homeostasis during pregnancy. Based on these results, we generated a conditional knockout mouse that lacks the suppressor of cytokine signaling-3 (SOCS3) only in leptin receptor-expressing cells and studied these animals during pregnancy. RESULTS:Among several genes involved in leptin resistance, only SOCS3 was increased in the hypothalamus of pregnant mice. Remarkably, SOCS3 deletion from leptin receptor-expressing cells prevented pregnancy-induced hyperphagia, body fat accumulation as well as leptin and insulin resistance without affecting the ability of the females to carry their gestation to term. Additionally, we found that SOCS3 conditional deletion protected females against long-term postpartum fat retention and streptozotocin-induced gestational diabetes. CONCLUSIONS:Our study identified the increased hypothalamic expression of SOCS3 as a key mechanism responsible for triggering pregnancy-induced leptin resistance and metabolic adaptations. These findings not only help to explain a common phenomenon of the mammalian physiology, but it may also aid in the development of approaches to prevent and treat gestational metabolic imbalances.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Zampieri TT,Ramos-Lobo AM,Furigo IC,Pedroso JA,Buonfiglio DC,Donato J Jrdoi
10.1016/j.molmet.2014.12.005subject
Has Abstractpub_date
2014-12-19 00:00:00pages
237-45issue
3issn
2212-8778pii
S2212-8778(14)00206-3journal_volume
4pub_type
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2019-02-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2013-12-14 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.molmet.2014.02.001
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pub_type: 杂志文章,评审
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更新日期:2018-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.molmet.2017.03.003
更新日期:2017-03-18 00:00:00
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pub_type: 杂志文章
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更新日期:2017-10-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2013-09-25 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.molmet.2019.09.014
更新日期:2019-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.molmet.2018.05.013
更新日期:2018-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2018-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.molmet.2016.05.001
更新日期:2016-05-10 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.molmet.2016.09.006
更新日期:2016-09-20 00:00:00
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doi:10.1016/j.molmet.2014.10.001
更新日期:2014-10-16 00:00:00
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更新日期:2018-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2018-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.molmet.2017.08.003
更新日期:2017-11-01 00:00:00