Prenatal influences on susceptibility to diet-induced obesity are mediated by altered neuroendocrine gene expression
Prenatal influences on susceptibility to diet-induced obesity are mediated by altered neuroendocrine gene expression
复制标题
DOI：
10.1677/joe.1.07017
复制
发表时间：
2007-04-01
影响因子：
4
通讯作者：
Fraser, Mhoyra
中科院分区：
文献类型：
--
作者：
Ikenasio-Thorpe, Bettina A.;Breier, Bernhard H.;Fraser, Mhoyra
肥胖症和2型糖尿病的发病率不断上升，已达到流行病的程度。有人提出，成年后发生代谢紊乱的风险受到环境因素的影响，这些因素在发育的早期阶段起作用。我们以前已经表明，产前和产后饮食环境之间的相互作用放大了饮食诱导肥胖的倾向，尽管机制尚不清楚。在本研究中，我们调查了产前营养不良和产后高脂肪营养对下丘脑食欲调节网络关键基因的相互作用。怀孕的Wistar大鼠在整个妊娠期（UN）自由进食（AD）或以AD摄入量的30%进食标准食物。从断奶开始，雌性AD和UN后代在研究的剩余时间内自由采食标准食物（ADC it = 8，UNHF n = 8）或高脂肪饮食（45% kcal脂肪; ADHF it = 8，UNHF n = 8）。在24周龄时，通过双能X射线吸收测定法分析评估身体组成，并从整个大鼠下丘脑提取总RNA。采用实时荧光定量PCR方法检测阿片黑素皮质素原（POMC）、神经肽Y（NPY）、刺鼠相关蛋白（AgRP）和OBRb基因mRNA水平的表达。我们的研究结果表明，出生后肥胖的放大发展作为一个结果之间的相互作用产前营养不良和出生后高脂肪营养。该表型还显示POMC、NPY、AgRP和OBRb基因表达的显著改变以及血浆瘦素和胰岛素两者的循环水平的升高。这些发现与预测性适应性反应假说一致，即胎儿期神经内分泌的发育可能是基于对出生后环境条件的预测。如果预期和实际情况不匹配，就会增加对饮食引起的肥胖的易感性。
The escalating rates of obesity and type 2 diabetes have reached pandemic proportions. It has been proposed that the risk of developing metabolic disorders in adult life is influenced by environmental factors, which operate during the early periods of development. We have previously shown that an interaction between the prenatal and the postnatal dietary environment amplifies the propensity towards diet-induced obesity, although the mechanisms are unclear. In the present study, we investigated the interaction between prenatal undernutrition and postnatal high-fat nutrition on key genes of the hypothalamic appetite regulatory network. pregnant Wistar rats were fed a standard chow diet either ad libitum (AD) or at 30% of AD intake throughout gestation (UN). From weaning, female AD and UN offspring were fed either a standard chow (ADC it = 8, UNC n = 8) or a high-fat diet (45% kcal as fat; ADHF it = 8, UNHF n = 8) ad libitum for the remainder of the study. At 24 weeks of age, body composition was assessed by dual energy X-ray absorptiometry analysis and total RNA was extracted from whole rat hypothalami. Real-time PCR was performed to characterise pro-opiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related protein (AgRP) and OBRb gene expression at the mRNA level. Our results demonstrate that the amplification of postnatal obesity develops as a consequence of an interaction between prenatal undernutrition and postnatal high-fat nutrition. This phenotype also shows significant alterations in POMC, NPY, AgRP and OBRb gene expression together with elevations in circulating, levels of both plasma leptin and insulin. These findings are consistent with the predictive adaptive response hypothesis that neuroendocrine development during fetal life may be based on predictions about postnatal environmental conditions. Increased susceptibility to diet-induced obesity develops if a mismatch between the anticipated and the actual conditions are encountered.