Dunlop Kristyn, Cedrone Megan, Staples James F, Regnault Timothy R H
Department of Physiology and Pharmacology, Western University, London, ON N6A-5C1, Canada.
Department of Biology, Western University, London, ON N6A 5B7, Canada.
Nutrients. 2015 Feb 12;7(2):1202-16. doi: 10.3390/nu7021202.
The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency.
子宫内环境作为导致成年后代谢疾病的一个因素，其重要性已在人类和动物研究中得到证实。在这篇综述中，我们探讨正常胎儿生长的中断如何影响骨骼肌代谢发育，最终导致胰岛素抵抗和胰岛素敏感性降低，而这是成年后代谢疾病的一个关键先兆。在与缺氧相关的子宫内生长受限（IUGR）病例中，胎儿无法充分发挥其生长潜力，往往会导致低出生体重（LBW），并且在出生后的早期，低出生体重个体的胰岛素信号通路会出现改变，这是胰岛素抵抗的一个关键先兆。在这篇综述中，我们将展示详细阐述IUGR中胰岛素抵抗经典发展过程的文献，同时也会讨论当受到出生后西式饮食的挑战时，这种发育受损如何可能导致成年后胰岛素抵抗的发展。考虑到骨骼肌在胰岛素抵抗发病机制中的重要作用，了解子宫内编程导致的骨骼肌胰岛素敏感性缺陷的起源以及它们如何与不良的出生后环境相互作用，是为胎盘功能不全的妊娠所生的低出生体重后代突出潜在治疗选择的重要一步。
