Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity.
Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity.
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DOI：
10.1523/jneurosci.2642-08.2008
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发表时间：
2008-11-12
期刊：
影响因子：
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通讯作者：
Leibowitz SF
中科院分区：
文献类型：
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作者：
Chang GQ;Gaysinskaya V;Karatayev O;Leibowitz SF
最近对成年和断奶大鼠的研究表明，膳食脂肪与循环脂质密切相关，可刺激参与控制食物摄入和体重的下丘脑肽的表达。在本研究中，我们研究了怀孕期间富含脂肪的饮食改变子宫内这些肽系统发育的可能性，在后代中产生神经元变化，这些变化在出生后没有饮食的情况下持续存在并具有长期后果。从胚胎第6天到出生后第15天（P15），高脂肪（HFD）与平衡饮食（BD）母鼠的后代表现出食欲肽，甘丙肽，脑啡肽和强啡肽的表达增加，在室旁核和食欲素和黑色素浓缩激素在穹窿周围外侧下丘脑。这些肽表达神经元的密度增加，在新生儿后代以及出生时交叉培养的P15后代BD上的母鼠中很明显，这使我们检查可能发生在子宫内的事件。在妊娠期间，HFD刺激胚胎下丘脑第三脑室的神经上皮细胞和神经元前体细胞的增殖。它还刺激了神经元的增殖和分化，以及它们向下丘脑区域的迁移，在下丘脑区域，最终有更大比例的新神经元表达促食欲肽。这种神经发生的增加与血液中脂质的显著增加密切相关，可能在断奶后后代中观察到的长期行为和生理变化中发挥作用，包括食物摄入量增加，对脂肪的偏好，高脂血症和体重增加。
Recent studies in adult and weanling rats show that dietary fat, in close association with circulating lipids, can stimulate expression of hypothalamic peptides involved in controlling food intake and body weight. In the present study, we examined the possibility that a fat-rich diet during pregnancy alters the development of these peptide systems in utero, producing neuronal changes in the offspring that persist postnatally in the absence of the diet and have long-term consequences. The offspring of dams on a high-fat (HFD) vs balanced diet (BD), from embryonic day 6 to postnatal day 15 (P15), showed increased expression of orexigenic peptides, galanin, enkephalin and dynorphin, in the paraventricular nucleus and orexin and melanin-concentrating hormone in the perifornical lateral hypothalamus. The increased density of these peptide-expressing neurons, evident in newborn offspring as well as P15 offspring cross-fostered at birth to dams on the BD, led us to examine events that might be occurring in utero. During gestation, the HFD stimulated the proliferation of neuroepithelial and neuronal precursor cells of the embryonic hypothalamic third ventricle. It also stimulated the proliferation and differentiation of neurons and their migration toward hypothalamic areas where ultimately a greater proportion of the new neurons expressed the orexigenic peptides. This increase in neurogenesis, closely associated with a marked increase in lipids in the blood, may have a role in producing the long-term behavioral and physiological changes observed in offspring after weaning, including an increase in food intake, preference for fat, hyperlipidemia, and higher body weight.