Embryo-transfer of the F2 postnatal calorie restricted female rat offspring into a control intra-uterine environment normalizes the metabolic phenotype.
Embryo-transfer of the F2 postnatal calorie restricted female rat offspring into a control intra-uterine environment normalizes the metabolic phenotype.
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DOI：
10.1016/j.metabol.2012.08.026
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发表时间：
2013-03
影响因子：
9.8
通讯作者：
Devaskar, Sherin U.
中科院分区：
文献类型：
--
作者：
Garg, Meena;Thamotharan, Manikkavasagar;Dai, Yun;Lee, Paul W. N.;Devaskar, Sherin U.
第一代（F1）雌性大鼠后代的出生后热量和生长限制（PNGR）导致与低胰岛素血症和葡萄糖刺激的胰岛素分泌（GSIS）减少相关的瘦和葡萄糖耐受表型。尽管在F1 PNGR雌性中不存在妊娠高血糖症，但据报道，自然出生的第二代（F2）PNGR雌性成年后代表现出肥胖、高血糖症伴胰岛素抵抗。本研究的目的是确定宫内环境对F2 PNGR雌性成年后代跨代表型表达的遗传力的作用。我们进行胚胎移植（ET）的F2胚胎从生育F1妊娠PNGR或对照（CON）的女性在对照受体大鼠母亲怀孕。采用稳定同位素测定葡萄糖代谢动力学。雌性F2 ET-PNGR的出生体重、出生后生长模式和白色脂肪组织与ET-CON相似。同样，未观察到基础葡萄糖和胰岛素浓度、GSIS、葡萄糖无效循环和葡萄糖清除率的差异。与F2 ET-CON相比，F2 ET-PNGR显示葡萄糖或肝葡萄糖产生（HGP）AUC无总体差异，高血糖症极轻微（p<0.04），这是由于仅在IVGTT的第一阶段观察到未抑制的内源性HGP（p<0.02）。我们的结论是，当胚胎转移的F2后代在正常的代谢环境中孕育时，F1代中GSIS减少的瘦，葡萄糖耐受和低胰岛素血症表型接近正常化。这一观察结果支持子宫内环境在改变跨代PNGR表型的遗传性中的作用。
Postnatal calorie and growth restriction (PNGR) in the first generation (F1) rat female offspring causes a lean and glucose tolerant phenotype associated with hypoinsulinemia and reduced glucose-stimulated insulin secretion (GSIS). Despite the absence of gestational hyperglycemia in the F1 PNGR female, naturally born second generation (F2) PNGR female adult offspring reportedly exhibit obesity, hyperglycemia with insulin resistance. The objective of this study was to determine the role of the intrauterine environment on the heritability of the trans-generational phenotypic expression in the F2 PNGR female adult offspring. We performed embryo transfer (ET) of the F2 embryos from the procreating F1 pregnant PNGR or control (CON) females to gestate in control recipient rat mothers. Employing stable isotopes glucose metabolic kinetics was determined. Birth weight, postnatal growth pattern and white adipose tissue in female F2 ET-PNGR were similar to ET-CON. Similarly, no differences in basal glucose and insulin concentrations, GSIS, glucose futile cycling and glucose clearance were seen. When compared to F2 ET-CON, F2 ET-PNGR showed no overall difference in glucose or hepatic glucose production (HGP) AUCs with minimal hyperglycemia (p<0.04) as a result of unsuppressed endogenous HGP (p<0.02) observed only during the first phase of IVGTT. We conclude that the lean, glucose tolerant and hypoinsulinemic phenotype with reduced GSIS in the F1 generation is near normalized when the embryo-transferred F2 offspring gestates in a normal metabolic environment. This observation supports a role for the intra-uterine environment in modifying the heritability of the trans-generational PNGR phenotype.
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DOI：
10.1097/01.mpg.0000302965.93546.b8
发表时间：
2007-12-01
影响因子：
2.9
作者：
Hay, William W., Jr.
通讯作者：
Hay, William W., Jr.
影响因子：
3.1
作者：
SZAFRANECK, J;PFAFFENBERGER, CD;HORNING, EC
通讯作者：
HORNING, EC
DOI：
10.1152/ajpendo.00516.2002
发表时间：
2003-05-01
影响因子：
5.1
作者：
Thamotharan, M;McKnight, RA;Devaskar, SU
通讯作者：
Devaskar, SU
DOI：
10.1152/ajpendo.00462.2006
发表时间：
2007-05-01
影响因子：
5.1
作者：
Thamotharan, Manikkavasagar;Garg, Meena;Devaskar, Sherin U.
通讯作者：
Devaskar, Sherin U.
影响因子：
158.5
作者：
Barker, DJP;Osmond, C;Eriksson, JG
通讯作者：
Eriksson, JG