Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction?
Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction?
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DOI：
10.3389/fnins.2015.00187
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发表时间：
2015-06-08
影响因子：
4.3
通讯作者：
D'Addario, Claudio
中科院分区：
文献类型：
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作者：
Cifani, Carlo;Di Bonaventura, Maria V. Micioni;D'Addario, Claudio
几个因素在肥胖(即行为、环境和遗传)中起作用，基因表达的表观遗传调控已成为肥胖易感性和发展的潜在贡献者。为了研究个体对体重增加/抵抗的敏感性，我们研究了几种参与控制肥胖(饮食诱导肥胖，DIO)和非肥胖(饮食抵抗，DR)大鼠在高脂饮食中能量平衡的下丘脑神经肽的基因转录调节。对高脂饮食暴露的大鼠进行了长达21周的跟踪调查。在高脂饮食暴露5周后，肥胖表型出现，我们观察到促食欲素神经肽Y(NPY)和过氧化物酶体增殖物激活受体γ(PPAR-y)基因选择性下调。没有观察到刺鼠相关蛋白(AgRP)的表达以及所有研究中的厌氧基因的变化。在长期高脂饮食暴露(21周)后，NPY和PPAR-y以及所研究的大部分基因在DIO和DR之间没有差异，但与DR大鼠相比，DIO大鼠厌食性阿片原-黑素皮质素(POMC)基因的表达较低。此外，我们还观察到NPY和POMC mRNA的变化与基因启动子DNA甲基化呈负相关。我们的发现表明，下丘脑肽基因调控的选择性改变可能有助于大鼠超重的发展，环境因素，如在这个动物模型中，可能通过表观遗传机制对这些变化起部分作用。
Several factors play a role in obesity (i.e., behavior, environment, and genetics) and epigenetic regulation of gene expression has emerged as a potential contributor in the susceptibility and development of obesity. To investigate the individual sensitivity to weight gain/resistance, we here studied gene transcription regulation of several hypothalamic neuropeptides involved in the control of energy balance in rats developing obesity (diet-induced obesity, DIO) or not (diet resistant, DR), when fed with a high fat diet. Rats have been followed up to 21 weeks of high fat diet exposure. After 5 weeks high fat diet exposure, the obese phenotype was developed and we observed a selective down-regulation of the orexigenic neuropeptide Y (NPY) and peroxisome proliferator-activated receptor gamma (PPAR-y) genes. No changes were observed in the expression of the agouti-related protein (AgRP), as well as for all the anorexigenic genes under study. After long-term high fat diet exposure (21 weeks), NPY and PPAR-y, as well as most of the genes under study, resulted not be different between DIO and DR, whereas a lower expression of the anorexigenic pro-opio-melanocortin (POMC) gene was observed in DIO rats when compared to DR rats. Moreover we observed that changes in NPY and POMC mRNA were inversely correlated with gene promoters DNA methylation. Our findings suggest that selective alterations in hypothalamic peptide genes regulation could contribute to the development of overweight in rats and that environmental factor, as in this animal model, might be partially responsible of these changes via epigenetic mechanism.