Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, Missouri, USA.
Division of Biological Sciences, University of Missouri, Columbia, Missouri, USA.
Biol Reprod. 2019 May 1;100(5):1356-1369. doi: 10.1093/biolre/ioz009.
We previously developed a model of gestational diabetes mellitus (GDM) in which dams exhibit glucose intolerance, insulin resistance, and reduced insulin response to glucose challenge only during pregnancy, without accompanying obesity. Here, we aimed to determine how lean gestational glucose intolerance affects offspring risk of metabolic dysfunction. One cohort of offspring was sacrificed at 19 weeks, and one at 31 weeks, with half of the second cohort placed on a high-fat, high-sucrose diet (HFHS) at 23 weeks. Exposure to maternal glucose intolerance increased weights of HFHS-fed offspring. Chow-fed offspring of GDM dams exhibited higher body fat percentages at 4, 12, and 20 weeks of age. At 28 weeks, offspring of GDM dams fed the HFHS but not the chow diet (CD) also had higher body fat percentages than offspring of controls (CON). Exposure to GDM increased the respiratory quotient (Vol CO2/Vol O2) in offspring. Maternal GDM increased adipose mRNA levels of peroxisome proliferator-activated receptor gamma (Pparg) and adiponectin (Adipoq) in 31-week-old CD-fed male offspring, and increased mRNA levels of insulin receptor (Insr) and lipoprotein lipase (Lpl) in 31-week-old male offspring on both diets. In liver at 31 weeks, mRNA levels of peroxisome proliferator-activated receptor alpha (Ppara) were elevated in CD-fed male offspring of GDM dams, and male offspring of GDM dams exhibited higher mRNA levels of Insr on both diets. Neither fasting insulin nor glucose tolerance was affected by exposure to GDM. Our findings show that GDM comprising glucose intolerance only during pregnancy programs increased adiposity in offspring, and suggests increased insulin sensitivity of subcutaneous adipose tissue.
我们之前建立了一种妊娠糖尿病（GDM）模型，其中母体仅在妊娠期间表现出葡萄糖耐量受损、胰岛素抵抗和对葡萄糖刺激的胰岛素反应降低，而没有伴随肥胖。在这里，我们旨在确定瘦型妊娠葡萄糖耐量受损如何影响后代代谢功能障碍的风险。一部分后代在 19 周时被处死，另一部分在 31 周时被处死，其中一半第二组在 23 周时接受高脂肪、高蔗糖饮食（HFHS）。暴露于母体葡萄糖耐量受损会增加 HFHS 喂养后代的体重。GDM 母鼠的 Chow 喂养后代在 4、12 和 20 周龄时体脂百分比更高。在 28 周时，GDM 母鼠喂养 HFHS 但不喂养 CD 的后代的体脂百分比也高于对照组（CON）的后代。暴露于 GDM 会增加后代的呼吸商（Vol CO2/Vol O2）。GDM 增加了 31 周龄 CD 喂养雄性后代脂肪组织中过氧化物酶体增殖物激活受体γ（Pparg）和脂联素（Adipoq）的 mRNA 水平，并增加了两种饮食中 31 周龄雄性后代胰岛素受体（Insr）和脂蛋白脂肪酶（Lpl）的 mRNA 水平。在 31 周龄时，GDM 母鼠喂养的 CD 雄性后代肝脏中过氧化物酶体增殖物激活受体α（Ppara）的 mRNA 水平升高，GDM 母鼠的雄性后代在两种饮食中均表现出更高的 Insr mRNA 水平。暴露于 GDM 并不影响空腹胰岛素或葡萄糖耐量。我们的研究结果表明，仅在妊娠期间出现葡萄糖耐量受损的 GDM 会使后代的肥胖程度增加，并提示皮下脂肪组织的胰岛素敏感性增加。
