Department of Animal Science, Texas A&M University, College Station, TX 77845, USA; Instituto de Investigaciones Agropecuarias, Región de Magallanes y la Antártica Chilena, Punta Arenas 6212707, Chile.
Department of Animal Science, Texas A&M University, College Station, TX 77845, USA.
Domest Anim Endocrinol. 2021 Jan;74:106556. doi: 10.1016/j.domaniend.2020.106556. Epub 2020 Oct 6.
Maternal nutrient restriction (NR) causes small for gestational age (SGA) offspring, which are at higher risk for accelerated postnatal growth and developing insulin resistance in adulthood. Skeletal muscle is essential for whole-body glucose metabolism, as 80% of insulin-mediated glucose uptake occurs in this tissue. Maternal NR can alter fetal skeletal muscle mass, expression of glucose transporters, insulin signaling, and myofiber type composition. It also leads to accumulation of intramuscular triglycerides (IMTG), which correlates to insulin resistance. Using a 50% NR treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the NR group. Thus, we classified those fetuses into NR(Non-SGA; n = 11) and NR(SGA; n = 11). The control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and gastrocnemius and soleus muscles were collected. In fetal plasma, total insulin was lower in NR(SGA) fetuses compared NR(Non-SGA) and control fetuses (P < 0.01), whereas total IGF-1 was lower in NR(SGA) fetuses compared with control fetuses (P < 0.05). Within gastrocnemius, protein expression of insulin receptor (INSRB; P < 0.05) and the glucose transporters, solute carrier family 2 member 1 and solute carrier family 2 member 4, was higher (P < 0.05) in NR(SGA) fetuses compared with NR(Non-SGA) fetuses; IGF-1 receptor protein was increased (P < 0.01) in NR(SGA) fetuses compared with control fetuses, and a lower (P < 0.01) proportion of type I myofibers (insulin sensitive and oxidative) was observed in SGA fetuses. For gastrocnemius muscle, the expression of lipoprotein lipase (LPL) messenger RNA (mRNA) was upregulated (P < 0.05) in both NR(SGA) and NR(Non-SGA) fetuses compared with control fetuses, whereas carnitine palmitoyltransferase 1B (CPT1B) mRNA was higher (P < 0.05) in NR(Non-SGA) fetuses compared with control fetuses, but there were no differences (P > 0.05) for protein levels of LPL or CPT1B. Within soleus, there were no differences (P > 0.05) for any characteristic except for the proportion of type I myofibers, which was lower (P < 0.05) in NR(SGA) fetuses compared with control fetuses. Accumulation of IMTG did not differ (P > 0.05) in gastrocnemius or soleus muscles. Collectively, the results indicate molecular differences between SGA and Non-SGA fetuses for most characteristics, suggesting that maternal NR induces a spectral phenotype for the metabolic programming of those fetuses.
母体营养限制（NR）会导致胎儿体重小于胎龄（SGA），这些胎儿在成年后更容易出现加速的产后生长和胰岛素抵抗。骨骼肌对于全身葡萄糖代谢至关重要，因为 80%的胰岛素介导的葡萄糖摄取发生在该组织中。NR 会改变胎儿骨骼肌的质量、葡萄糖转运蛋白的表达、胰岛素信号以及肌纤维类型组成。它还会导致肌肉内甘油三酯（IMTG）的积累，这与胰岛素抵抗有关。在绵羊中，我们使用从妊娠第 35 天到第 135 天的 50%NR 处理，通常会在 NR 组中观察到胎儿体重的光谱表型。因此，我们将这些胎儿分为 NR（非 SGA；n=11）和 NR（SGA；n=11）。对照组（n=12）在整个怀孕期间接受 100%的营养需求。在妊娠第 135 天，收集胎儿血浆和比目鱼肌和跖肌。在胎儿血浆中，NR（SGA）胎儿的总胰岛素水平低于 NR（非 SGA）和对照组胎儿（P<0.01），而 NR（SGA）胎儿的总 IGF-1 水平低于对照组胎儿（P<0.05）。在比目鱼肌中，胰岛素受体（INSRB；P<0.05）和葡萄糖转运蛋白溶质载体家族 2 成员 1 和溶质载体家族 2 成员 4 的蛋白质表达在 NR（SGA）胎儿中更高（P<0.05）；NR（SGA）胎儿的 IGF-1 受体蛋白增加（P<0.01），而 SGA 胎儿的 I 型肌纤维（胰岛素敏感和氧化）比例较低（P<0.01）。对于比目鱼肌，脂蛋白脂肪酶（LPL）信使 RNA（mRNA）的表达在 NR（SGA）和 NR（非 SGA）胎儿中均高于对照组胎儿（P<0.05），而肉碱棕榈酰转移酶 1B（CPT1B）mRNA 在 NR（非 SGA）胎儿中高于对照组胎儿（P<0.05），但 LPL 或 CPT1B 的蛋白水平没有差异（P>0.05）。在跖肌中，除 I 型肌纤维的比例较低外（P<0.05），没有其他特征存在差异（P>0.05）。IMTG 的积累在比目鱼肌或跖肌中没有差异（P>0.05）。总的来说，结果表明 SGA 和非 SGA 胎儿在大多数特征上存在分子差异，这表明母体 NR 对这些胎儿的代谢编程诱导了光谱表型。
