Domestic Animal Endocrinology ( IF 2.1 ) Pub Date : 2020-10-06 , DOI: 10.1016/j.domaniend.2020.106556 C Sandoval 1 , K Askelson 2 , C A Lambo 3 , K A Dunlap 2 , M C Satterfield 2
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.
中文翻译:
母体营养限制对 SGA 和非 SGA 绵羊胎儿骨骼肌中葡萄糖转运蛋白(SLC2A4 和 SLC2A1)表达和胰岛素信号传导的影响
母体营养限制 (NR) 会导致小于胎龄 (SGA) 的后代出现出生后加速生长和成年期出现胰岛素抵抗的风险更高。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。母体 NR 可以改变胎儿骨骼肌质量、葡萄糖转运蛋白的表达、胰岛素信号传导和肌纤维类型组成。它还导致与胰岛素抵抗相关的肌内甘油三酯 (IMTG) 的积累。从妊娠日 (GD) 35 到 GD 135 在绵羊中使用 50% NR 处理,我们定期观察 NR 组内胎儿体重的光谱表型。因此,我们将这些胎儿分为 NR(Non-SGA; n = 11) 和 NR(SGA; n = 11)。对照组(n = 12)在整个怀孕期间接受了 100% 的营养需求。在 GD 135 时,收集胎儿血浆、腓肠肌和比目鱼肌。在胎儿血浆中,与 NR(Non-SGA) 和对照胎儿相比,NR(SGA) 胎儿的总胰岛素较低。P < 0.01),而 NR(SGA) 胎儿的总 IGF-1 低于对照胎儿 ( P < 0.05)。在腓肠肌内,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 的蛋白表达在 NR(SGA) 胎儿中高于 NR (P < 0.05)(P < 0.05) (非 SGA)胎儿;与对照胎儿相比,NR(SGA) 胎儿的IGF-1 受体蛋白增加 ( P < 0.01),并且在 SGA 胎儿中观察到 I 型肌纤维(胰岛素敏感性和氧化性)比例较低 ( P < 0.01)。对于腓肠肌,脂蛋白脂肪酶(LPL)的表达) NR(SGA) 和 NR(Non-SGA) 胎儿与对照胎儿相比,信使 RNA (mRNA) 均上调 ( P < 0.05),而肉碱棕榈酰转移酶 1B ( CPT1B ) mRNA在 NR( P < 0.05) 中更高 ( P < 0.05)非 SGA) 胎儿与对照胎儿相比,LPL 或 CPT1B 的蛋白质水平没有差异 ( P > 0.05)。在比目鱼肌内,除了 I 型肌纤维的比例,NR(SGA) 胎儿与对照胎儿相比,I 型肌纤维的比例较低 ( P < 0.05)外,其他任何特征均无差异 ( P > 0.05) 。IMTG的积累没有差异(P> 0.05) 在腓肠肌或比目鱼肌中。总的来说,结果表明 SGA 和非 SGA 胎儿在大多数特征上的分子差异,表明母体 NR 诱导了这些胎儿代谢程序的光谱表型。