Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
J Neuroendocrinol. 2010 Aug;22(8):905-14. doi: 10.1111/j.1365-2826.2010.02005.x. Epub 2010 Apr 6.
Maternal obesity has long-term consequences for the development of hypothalamic neurones involved in energy homeostasis and the metabolic profile in offspring. In the present study, we compared the effects of maternal obesity induced by longstanding high-fat diet (HFD) with milder postnatal overfeeding during suckling induced by litter size reduction. Female Sprague-Dawley rats consumed chow (C) or HFD. On postnatal day 1, litters from chow dams were adjusted to three per dam (small litter, CS) versus 12 control (normal litter, CN). Litters from HFD dams were adjusted to 12 per dam and fed HFD after weaning to induce obesity (HN). Thus, two degrees of maternal overnutrition were produced (CS and HN). To test whether postweaning diet can amplify the effects of maternal obesity, male offspring weaned onto chow or HFD were followed to 21 weeks. Maternal postnatal overnutrition (CS) and HFD-induced maternal obesity (HN) increased body weight and fat mass in offspring compared to those from control dams (CN). Significant glucose intolerance was induced by both degrees of maternal overnutrition, but only in offspring consuming HFD. HFD-induced maternal obesity (HN) was linked to increased offspring leptin, insulin, lipids, insulin resistance and hyperphagia, and was exaggerated by postweaning HFD. No effect of maternal postnatal overnutrition (CS) was seen on these parameters. Hypothalamic signal transducer and activator of transcription-3 and suppressor of cytokine signalling-3 mRNA were significantly elevated by maternal HFD (HN) in the HFD-fed offspring. The data obtained suggest that even mild maternal overnutrition (CS) led to increased adiposity, glucose intolerance and altered brain appetite regulators in offspring. A greater impact of HFD-induced maternal obesity was evident. Marked additive effects were observed when animals consumed a HFD postweaning.
母体肥胖会对后代参与能量平衡和代谢特征的下丘脑神经元的发育产生长期影响。在本研究中，我们比较了长期高脂肪饮食（HFD）诱导的母体肥胖与哺乳期通过减少产仔数引起的轻度产后过度喂养对后代的影响。雌性 Sprague-Dawley 大鼠分别摄入标准饮食（C）或 HFD。产后第 1 天，来自标准饮食母鼠的窝仔数调整为每窝 3 只（小窝，CS），而来自正常饮食母鼠的窝仔数为 12 只（正常窝仔，CN）。来自 HFD 母鼠的窝仔数调整为每窝 12 只，断奶后喂食 HFD 以诱导肥胖（HN）。因此，产生了两种程度的母体营养过剩（CS 和 HN）。为了测试产后饮食是否可以放大母体肥胖的影响，断奶后继续给予雄性后代标准饮食或 HFD，直至 21 周。与来自对照母鼠（CN）的后代相比，产后营养过剩（CS）和 HFD 诱导的母体肥胖（HN）增加了后代的体重和脂肪量。两种程度的母体营养过剩均导致明显的葡萄糖不耐受，但仅在摄入 HFD 的后代中发生。HFD 诱导的母体肥胖（HN）与后代瘦素、胰岛素、脂质、胰岛素抵抗和多食增加有关，且这种情况在断奶后摄入 HFD 时更为严重。产后营养过剩（CS）对这些参数没有影响。在 HFD 喂养的后代中，HFD 诱导的母体肥胖（HN）导致下丘脑信号转导子和转录激活子 3 和细胞因子信号转导抑制因子 3 的 mRNA 显著升高。数据表明，即使是轻度的母体营养过剩（CS）也会导致后代肥胖、葡萄糖不耐受和改变大脑食欲调节剂。HFD 诱导的母体肥胖的影响更大。当动物断奶后摄入 HFD 时，观察到明显的叠加效应。
