Glastras Sarah J, Chen Hui, McGrath Rachel T, Zaky Amgad A, Gill Anthony J, Pollock Carol A, Saad Sonia
Department of Medicine, Kolling Institute, University of Sydney, NSW, Australia.
Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, NSW, Australia.
Sci Rep. 2016 Mar 23;6:23525. doi: 10.1038/srep23525.
Maternal obesity is associated with an increased risk of chronic disease in offspring, including type 2 diabetes (T2D). Exendin-4 (Exd-4) activates the glucagon like peptide-1 (GLP-1) receptor thereby decreasing serum glucose levels and body weight. In addition, Exd-4 has been shown to reduce renal and cardiac complications in experimental models of T2D. We hypothesized that treatment with Exd-4 would ameliorate the detrimental effects of maternal and diet-induced obesity on renal characteristics in offspring. Female Sprague-Dawley rats were fed either normal or high-fat diet (HFD) for 6 weeks prior to pregnancy, during pregnancy and lactation, and their offspring were weaned to normal or HFD. The offspring were randomized to Exd-4 or placebo from weaning and their kidneys harvested at Week 9. We found that the kidneys of offspring from obese mothers, regardless of postnatal diet, had significantly increased markers of inflammation, oxidative stress and fibrosis. Exd-4 ameliorated the negative renal effects of maternal obesity and in particular, reduced renal inflammation, oxidative stress and fibrosis. In conclusion, maternal obesity has persisting effects on renal structure in the offspring. GLP-1 analogues are potentially useful for protecting against the deleterious effects of maternal obesity on renal physiology in offspring.
母体肥胖与后代患慢性疾病的风险增加有关，包括2型糖尿病（T2D）。艾塞那肽-4（Exd-4）激活胰高血糖素样肽-1（GLP-1）受体，从而降低血糖水平和体重。此外，在T2D实验模型中，Exd-4已被证明可减少肾脏和心脏并发症。我们推测，Exd-4治疗可改善母体和饮食诱导的肥胖对后代肾脏特征的有害影响。在怀孕前、怀孕期间和哺乳期，对雌性斯普拉格-道利大鼠喂食正常或高脂饮食（HFD）6周，其后代断奶后喂食正常或HFD。后代从断奶开始随机分为Exd-4组或安慰剂组，并在第9周采集肾脏。我们发现，无论出生后饮食如何，肥胖母亲后代的肾脏炎症、氧化应激和纤维化标志物均显著增加。Exd-4改善了母体肥胖对肾脏的负面影响，特别是减少了肾脏炎症、氧化应激和纤维化。总之，母体肥胖对后代肾脏结构有持续影响。GLP-1类似物可能有助于预防母体肥胖对后代肾脏生理的有害影响。
