Breton Christophe, Lukaszewski Marie-Amélie, Risold Pierre-Yves, Enache Mihaela, Guillemot Johann, Rivière Guillaume, Delahaye Fabien, Lesage Jean, Dutriez-Casteloot Isabelle, Laborie Christine, Vieau Didier
Neurosciences et Physiologie Adaptatives, Université de Lille I, Villeneuve d'Ascq, France.
Am J Physiol Endocrinol Metab. 2009 Mar;296(3):E462-72. doi: 10.1152/ajpendo.90740.2008. Epub 2008 Dec 16.
Epidemiological studies suggest that maternal undernutrition predisposes the offspring to development of energy balance metabolic pathologies in adulthood. Using a model of a prenatal maternal 70% food-restricted diet (FR30) in rats, we evaluated peripheral parameters involved in nutritional regulation, as well as the hypothalamic appetite-regulatory system, in nonfasted and 48-h-fasted adult offspring. Despite comparable glycemia in both groups, mild glucose intolerance, with a defect in glucose-induced insulin secretion, was observed in FR30 animals. They also exhibited hyperleptinemia, despite similar visible fat deposits. Using semiquantitative RT-PCR, we observed no basal difference of hypothalamic proopiomelanocortin (POMC) and neuropeptide Y (NPY) gene expression, but a decrease of the OB-Rb and an increase of insulin receptor mRNA levels, in FR30 animals. These animals also exhibited basal hypercorticosteronemia and a blunted increase of corticosterone in fasted compared with control animals. After fasting, FR30 animals showed no marked reduction of POMC mRNA levels or intensity of beta-endorphin-immunoreactive fiber projections. By contrast, NPY gene expression and immunoreactive fiber intensity increased. FR30 rats also displayed subtle alterations of food intake: body weight-related food intake was higher and light-dark phase rhythm and refeeding time course were modified after fasting. At rest, in the morning, hyperinsulinemia and a striking increase in the number of c-Fos-containing cells in the arcuate nucleus were observed. About 30% of the c-Fos-expressing cells were POMC neurons. Our data suggest that maternal undernutrition differently programs the long-term appetite-regulatory system of offspring, especially the response of POMC neurons to energy status and food intake rhythm.
流行病学研究表明，孕期母亲营养不足会使后代在成年后易患能量平衡代谢疾病。我们采用大鼠孕期母亲70%食物限制饮食（FR30）模型，评估了非禁食和禁食48小时的成年后代中参与营养调节的外周参数以及下丘脑食欲调节系统。尽管两组血糖水平相当，但在FR30组动物中观察到轻度葡萄糖不耐受以及葡萄糖诱导的胰岛素分泌缺陷。尽管可见脂肪沉积相似，但它们也表现出高瘦素血症。通过半定量逆转录聚合酶链反应，我们观察到FR30组动物下丘脑阿黑皮素原（POMC）和神经肽Y（NPY）基因表达无基础差异，但OB-Rb减少，胰岛素受体mRNA水平增加。与对照动物相比，这些动物还表现出基础高皮质酮血症以及禁食时皮质酮的增加减弱。禁食后，FR30组动物POMC mRNA水平或β-内啡肽免疫反应性纤维投射强度无明显降低。相比之下，NPY基因表达和免疫反应性纤维强度增加。FR30大鼠的食物摄入量也有细微变化：与体重相关的食物摄入量更高，禁食后明暗周期节律和再进食时间进程发生改变。在早晨休息时，观察到高胰岛素血症以及弓状核中含c-Fos细胞数量显著增加。约30%表达c-Fos的细胞是POMC神经元。我们的数据表明，孕期母亲营养不足对后代的长期食欲调节系统产生不同的编程影响，尤其是POMC神经元对能量状态和食物摄入节律的反应。
