Maternal prenatal undernutrition alters the response of POMC neurons to energy status variation in adult male rat offspring
Maternal prenatal undernutrition alters the response of POMC neurons to energy status variation in adult male rat offspring
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DOI：
10.1152/ajpendo.90740.2008
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发表时间：
2009-03-01
影响因子：
5.1
通讯作者：
Vieau, Didier
中科院分区：
文献类型：
--
作者：
Breton, Christophe;Lukaszewski, Marie-Amelie;Vieau, Didier
Breton C，Lukaszewski M，Risold PY，Enache M，Guillemot J，Riviere G，Delahaye F，Lesage J，Dutriez-Casteloot I，Laborie C，Vieau D。AM J生理学内分泌代谢酶296：E462-E472,2009。首次发表于2008年12月16日；doi:10.1152/ajpendo.90740.2008.-Epidemiological的研究表明，母亲营养不良使后代在成年后容易出现能量平衡的代谢病理。使用孕期70%食物限制饮食(FR30)的大鼠模型，我们评估了非禁食和禁食48小时的成年后代参与营养调节的外周参数以及下丘脑的食欲调节系统。尽管两组的血糖水平相当，但在FR30动物中观察到了轻度葡萄糖耐量异常，并伴有葡萄糖诱导的胰岛素分泌缺陷。他们也表现出高瘦素血症，尽管有相似的可见脂肪沉积。用半定量RT-PCR方法观察到FR30大鼠下丘脑前阿片黑素皮质素(POMC)和神经肽Y(NPY)基因表达无基础差异，但OB-Rb基因表达减少，胰岛素受体基因表达水平升高。与对照组动物相比，这些动物还表现出基础高皮质酮血症和空腹时皮质酮的缓慢增加。禁食后，FR30动物的POMC mRNA水平或β-内啡肽免疫反应纤维投射强度没有明显降低。相反，NPY基因表达和免疫反应纤维强度增加。FR30大鼠也表现出摄食量的细微变化：禁食后与体重相关的摄食量增加，明暗相节律和再摄食时间进程改变。清晨休息时，可观察到高胰岛素血症和弓状核内含c-Fos的细胞数量显著增加。约30%的c-Fos表达细胞为POMC神经元。我们的数据表明，母亲营养不良对后代的长期食欲调节系统有不同的编程，特别是POMC神经元对能量状态和食物摄取节奏的反应。
Breton C, Lukaszewski M, Risold PY, Enache M, Guillemot J, Riviere G, Delahaye F, Lesage J, Dutriez-Casteloot I, Laborie C, Vieau D. Maternal prenatal undernutrition alters the response of POMC neurons to energy status variation in adult male rat offspring. Am J Physiol Endocrinol Metab 296: E462-E472, 2009. First published December 16, 2008; doi:10.1152/ajpendo.90740.2008.-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.