Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
Department of Veterans Affairs Tennessee Valley, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Mol Metab. 2019 Jul;25:73-82. doi: 10.1016/j.molmet.2019.03.010. Epub 2019 Apr 12.
In humans, offspring of women who are overweight or obese are more likely to develop metabolic disease later in life. Studies in lower animal species reveal that a calorically-dense maternal diet is associated with alterations in islet cell mass and function. The long-term effects of maternal diet on the structure and function of offspring islets with characteristics similar to humans are unknown. We used a well-established non-human primate (NHP) model to determine the consequences of exposure to Western-Style Diet (WSD) in utero and during lactation on islet cell mass and function in the offspring.
Female Japanese Macaques (Macaca fuscata) were fed either control (CTR) or WSD before and throughout pregnancy and lactation. Offspring were weaned onto CTR or WSD to generate four different groups based on maternal/offspring diets: CTR/CTR, WSD/CTR, CTR/WSD, and WSD/WSD. Offspring were analyzed at three years of age. Pancreatic tissue sections were immunolabelled to measure α- and β-cell mass and proliferation as well as islet vascularization. Live islets were also isolated to test the effects of WSD-exposure on islet function ex vivo. Offspring glucose tolerance was correlated with various maternal characteristics.
α-cell mass was reduced as a result of maternal WSD exposure. α-cell proliferation was reduced in response to offspring WSD. Islet vasculature did not differ among the diet groups. Islets from WSD/CTR offspring secreted a greater amount of insulin in response to glucose ex vivo. We also found that maternal glucose tolerance and parity correlated with offspring glucose tolerance.
Maternal WSD exposure results in persistently decreased α-cell mass in the three-year old offspring. WSD/CTR islets secreted greater amounts of insulin ex vivo, suggesting that these islets are primed to hyper-secrete insulin under certain metabolic stressors. Although WSD did not induce overt impaired glucose tolerance in dams or offspring, offspring born to mothers with higher glucose excursions during a glucose tolerance test were more likely to also show higher glucose excursions.
在人类中，超重或肥胖女性的后代在以后的生活中更有可能患上代谢疾病。在较低等动物物种中的研究表明，高热量的母体饮食与胰岛细胞数量和功能的改变有关。母体饮食对具有类似人类特征的后代胰岛结构和功能的长期影响尚不清楚。我们使用了一种成熟的非人类灵长类动物（NHP）模型，以确定在子宫内和哺乳期暴露于西式饮食（WSD）对后代胰岛细胞数量和功能的影响。
雌性日本猕猴（Macaca fuscata）在怀孕和哺乳期前及整个哺乳期分别喂食对照（CTR）或 WSD。后代在断奶后分别喂食 CTR 或 WSD，根据母代/子代的饮食分为四组：CTR/CTR、WSD/CTR、CTR/WSD 和 WSD/WSD。在三岁时分析后代。胰腺组织切片免疫标记以测量α-和β-细胞数量和增殖以及胰岛血管化。还分离了活胰岛以测试 WSD 暴露对胰岛功能的影响。后代的葡萄糖耐量与各种母代特征相关。
由于母体 WSD 暴露，α-细胞数量减少。α-细胞增殖减少以响应后代 WSD。胰岛血管化在饮食组之间没有差异。WSD/CTR 后代的胰岛在体外对葡萄糖的反应中分泌更多的胰岛素。我们还发现，母体的葡萄糖耐量和产次与后代的葡萄糖耐量相关。
母体 WSD 暴露导致三岁后代的α-细胞数量持续减少。WSD/CTR 胰岛在体外分泌更多的胰岛素，这表明这些胰岛在某些代谢应激下更容易过度分泌胰岛素。尽管 WSD 没有在母代或后代中引起明显的葡萄糖耐量受损，但在葡萄糖耐量测试中葡萄糖波动较大的母代所生的后代更有可能表现出更高的葡萄糖波动。
