Morris M J, Chen H
Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Int J Obes (Lond). 2009 Jan;33(1):115-22. doi: 10.1038/ijo.2008.213. Epub 2008 Nov 4.
Key appetite regulators and their receptors are already present in the fetal hypothalamus, and may respond to hormones such as leptin. Intrauterine food restriction or hyperglycemia can reprogram these circuits, possibly predisposing individuals to adverse health outcomes in adulthood. Given the global obesity epidemic, maternal overweight and obesity is becoming more prevalent. Earlier, we observed rapid growth of pups from obese dams during the suckling period. However, it is unclear whether this is because of alterations in leptin and hypothalamic appetite regulators at birth.
Female Sprague-Dawley rats were fed palatable high-fat diet (HFD) or chow for 5 weeks to induce obesity before mating. The same diet continued during gestation. At day 1, after birth, plasma and hypothalamus were collected from male and female pups.
Body weight and organ mass were recorded. Leptin and insulin levels were measured in the plasma by radioimmunoassay. Hypothalamic mRNA expression of neuropeptide-Y (NPY), pro-opiomelanocortin, leptin receptor and its downstream signal, STAT3 (signal transducer and activator of transcription 3), were measured using real-time PCR.
Body and organ weights of pups from obese dams were similar to those from lean dams, across both genders. However, plasma leptin levels were significantly lower in offspring from obese dams (male: 0.53+/-0.13 vs 1.05+/-0.21 ng ml(-1); female: 0.33+/-0.09 vs 2.12+/-0.57 ng ml(-1), respectively; both P<0.05). Hypothalamic mRNA expression of NPY, pro-opiomelanocortin, leptin receptor and STAT3 were also significantly lower in pups from obese dams.
Long-term maternal obesity, together with lower leptin levels in pups from obese dams may contribute to the lower expression of key appetite regulators on day 1 of life, suggesting altered intrauterine neuron development in response to intrauterine overnutrition, which may contribute to eating disorders later in life.
关键食欲调节因子及其受体在胎儿下丘脑就已存在，且可能对瘦素等激素产生反应。子宫内食物限制或高血糖会使这些回路重新编程，可能使个体成年后易出现不良健康结局。鉴于全球肥胖流行，孕妇超重和肥胖正变得越来越普遍。此前，我们观察到肥胖母鼠的幼崽在哺乳期生长迅速。然而，尚不清楚这是否是由于出生时瘦素和下丘脑食欲调节因子的改变所致。
对雌性斯普拉格-道利大鼠在交配前喂食美味高脂饮食（HFD）或普通饲料5周以诱导肥胖。妊娠期间继续相同饮食。出生后第1天，从雄性和雌性幼崽中采集血浆和下丘脑。
记录体重和器官质量。通过放射免疫分析法测量血浆中的瘦素和胰岛素水平。使用实时PCR测量下丘脑神经肽Y（NPY）、阿黑皮素原、瘦素受体及其下游信号STAT3（信号转导和转录激活因子3）的mRNA表达。
肥胖母鼠的幼崽无论雌雄，其体重和器官重量与瘦母鼠的幼崽相似。然而，肥胖母鼠后代的血浆瘦素水平显著较低（雄性：0.53±0.13对1.05±0.21 ng/ml；雌性：0.33±0.09对2.12±0.57 ng/ml，均P<0.05）。肥胖母鼠幼崽下丘脑NPY、阿黑皮素原、瘦素受体和STAT3的mRNA表达也显著较低。
长期母体肥胖，以及肥胖母鼠幼崽较低的瘦素水平，可能导致出生第1天关键食欲调节因子表达降低，提示子宫内神经元发育因子宫内营养过剩而改变，这可能导致日后出现饮食失调。
