Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat.
Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat.
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DOI：
10.1371/journal.pone.0185272
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Myers DA
中科院分区：
文献类型：
--
作者：
Vargas VE;Gurung S;Grant B;Hyatt K;Singleton K;Myers SM;Saunders D;Njoku C;Towner R;Myers DA
缺乏妊娠缺氧对新生儿瘦素激增、下丘脑弓状核（ARH）投射和食欲的影响，这些影响可能有助于后代肥胖的编程。我们检测了Sprague-Dawley大鼠妊娠15-19天12%O2对断奶后食欲、MRI脂肪沉积、脂肪组织细胞因子表达、新生儿瘦素激增、ARH对外源性瘦素的反应以及雄性后代对高脂（HFD）或对照饮食（CD）反应时αMSH向室旁核（PVN）投射的影响。当从出生后5-8周开始喂食HFD时，常氧（NMX）和缺氧（HPX）后代表现出食物摄入量增加;与CD上的NMX后代相比，CD上的HPX后代从5-7周开始食物摄入量增加。HFD的HPX后代在23周内保持高吞噬性。喂食CD或HFD的4-12周龄HPX与NMX母鼠的后代体重相同。到14-23周龄时，喂食CD或HFD的HPX后代以及喂食HFD的雄性NMX后代比喂食CD的NMX后代更重。喂食CD的HPX后代表现出腹部肥胖（MRI）增加，这是由HFD放大的。喂食HFD的HPX后代表现出最高的腹部脂肪细胞因子表达。与NMX幼崽相比，HPX雄性后代从产后第6天（PN）到第14天的血浆瘦素更高。在PN 16，与NMX幼仔相比，HPX后代在ARH中表现出基础c-Fos标记细胞增加。在PN 16时，瘦素增加NMX而非HPX后代ARH中的c-Fos染色。PN 16时，HPX后代PVN中的αMSH纤维少于NMX后代。总之，妊娠期缺氧会影响ARH的发展，导致摄食过多，导致对照饮食的成人肥胖，并因HFD而加重。
The effect of gestational hypoxia on the neonatal leptin surge, development of hypothalamic arcuate nuclei (ARH) projections and appetite that could contribute to the programming of offspring obesity is lacking. We examined the effect of 12% O2 from gestational days 15–19 in the Sprague-Dawley rat on post-weaning appetite, fat deposition by MRI, adipose tissue cytokine expression, the neonatal leptin surge, ARH response to exogenous leptin, and αMSH projections to the paraventricular nucleus (PVN) in response to a high fat (HFD) or control diet (CD) in male offspring. Normoxia (NMX) and Hypoxia (HPX) offspring exhibited increased food intake when fed a HFD from 5–8 weeks post-birth; HPX offspring on the CD had increased food intake from weeks 5–7 vs. NMX offspring on a CD. HPX offspring on a HFD remained hyperphagic through 23 weeks. Body weight were the same between offspring from HPX vs. NMX dams from 4–12 weeks of age fed a CD or HFD. By 14–23 weeks of age, HPX offspring fed the CD or HFD as well as male NMX offspring fed the HFD were heavier vs. NMX offspring fed the CD. HPX offspring fed a CD exhibited increased abdominal adiposity (MRI) that was amplified by a HFD. HPX offspring fed a HFD exhibited the highest abdominal fat cytokine expression. HPX male offspring had higher plasma leptin from postnatal day (PN) 6 through 14 vs. NMX pups. HPX offspring exhibited increased basal c-Fos labeled cells in the ARH vs. NMX pups on PN16. Leptin increased c-Fos staining in the ARH in NMX but not HPX offspring at PN16. HPX offspring had fewer αMSH fibers in the PVN vs. NMX offspring on PN16. In conclusion, gestational hypoxia impacts the developing ARH resulting in hyperphagia contributing to adult obesity on a control diet and exacerbated by a HFD.