Department of Integrative Biology & Physiology, University of Minnesota, Minneapolis, MN, United States.
Department of Pediatrics, Division of Diabetes, Endocrinology, and Metabolism, University of Michigan Medical School, Ann Arbor, MI, United States.
Front Endocrinol (Lausanne). 2022 Jan 17;12:780300. doi: 10.3389/fendo.2021.780300. eCollection 2021.
The risk of obesity in adulthood is subject to programming in the womb. Maternal obesity contributes to programming of obesity and metabolic disease risk in the adult offspring. With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of maternal high-fat diet (HFD) during pregnancy on offspring's metabolic heath trajectory. In the present study, we determined the long-term metabolic outcomes on adult male and female offspring of dams fed with HFD during pregnancy. C57BL/6J dams were fed either Ctrl or 60% Kcal HFD for 4 weeks before and throughout pregnancy, and we tested glucose homeostasis in the adult offspring. Both Ctrl and HFD-dams displayed increased weight during pregnancy, but HFD-dams gained more weight than Ctrl-dams. Litter size and offspring birthweight were not different between HFD-dams or Ctrl-dams. A significant reduction in random blood glucose was evident in newborns from HFD-dams compared to Ctrl-dams. Islet morphology and alpha-cell fraction were normal but a reduction in beta-cell fraction was observed in newborns from HFD-dams compared to Ctrl-dams. During adulthood, male offspring of HFD-dams displayed comparable glucose tolerance under normal chow. Male offspring re-challenged with HFD displayed glucose intolerance transiently. Adult female offspring of HFD-dams demonstrated normal glucose tolerance but displayed increased insulin resistance relative to controls under normal chow diet. Moreover, adult female offspring of HFD-dams displayed increased insulin secretion in response to high-glucose treatment, but beta-cell mass were comparable between groups. Together, these data show that maternal HFD at pre-conception and during gestation predisposes the female offspring to insulin resistance in adulthood.
成年肥胖的风险受到子宫内编程的影响。母体肥胖导致成年后代肥胖和代谢疾病风险的编程。随着生育年龄妇女肥胖的患病率不断增加，有必要了解母体高脂肪饮食（HFD）在怀孕期间对后代代谢健康轨迹的影响。在本研究中，我们确定了在怀孕期间接受 HFD 喂养的母鼠的成年雄性和雌性后代的长期代谢结果。C57BL/6J 母鼠在怀孕前和怀孕期间分别接受对照或 60%卡路里 HFD 喂养 4 周，我们测试了成年后代的葡萄糖稳态。对照和 HFD 喂养的母鼠在怀孕期间体重均增加，但 HFD 喂养的母鼠比对照喂养的母鼠体重增加更多。HFD 喂养的母鼠或对照喂养的母鼠的窝仔数和仔鼠出生体重没有差异。与对照喂养的母鼠相比，HFD 喂养的母鼠的新生仔鼠随机血糖明显降低。与对照喂养的母鼠相比，HFD 喂养的母鼠的新生仔鼠胰岛形态和 alpha 细胞分数正常，但 beta 细胞分数减少。成年雄性后代在正常饮食下的葡萄糖耐量与 HFD 喂养的母鼠相似。HFD 喂养的雄性后代重新接受 HFD 挑战时表现出短暂的葡萄糖不耐受。HFD 喂养的母鼠的成年雌性后代表现出正常的葡萄糖耐量，但在正常饮食下表现出相对于对照组的胰岛素抵抗增加。此外，HFD 喂养的母鼠的成年雌性后代在高葡萄糖处理下表现出胰岛素分泌增加，但两组之间的 beta 细胞质量相当。总之，这些数据表明，母体 HFD 在受孕前和怀孕期间使雌性后代易患成年期的胰岛素抵抗。
