论文标题：Transgenerational transmission of hedonic behaviors and metabolic phenotypes induced by maternal overnutrition
期刊：
作者：Gitalee Sarker, Rebecca Berrens, Judith von Arx, Pawel Pelczar, Wolf Reik, Christian Wolfrum & Daria Peleg-Raibstein
发表时间：2018/10/12
数字识别码：10.1038/s41398-018-0243-2
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原文作者：Gitalee Sarker, Rebecca Berrens, Judith von Arx, Pawel Pelczar, Wolf Reik, Christian Wolfrum & Daria Peleg-Raibstein
最近发表在Translational Psychiatry上的研究表明，雌性小鼠的高脂肪饮食可以影响三代子孙的肥胖、胰岛素抵抗和类成瘾性行为。
来自瑞士苏黎世联邦理工学院的研究者发现，在孕期前、孕中和孕期后进行过高脂饮食的小鼠，其第二代后代——即孙辈——会表现出对药物敏感度提高、对药物有偏好等类成瘾性行为，同时还会出现肥胖相关的特征，如新陈代谢的变化。第三代后代（即曾孙辈）中，作者观察到一些性别差异，只有雌性有类成瘾性行为，只有雄性有肥胖特征。
虽然最初的雌鼠自身并未肥胖，后几代小鼠也并未进行过高脂肪饮食，但上述情况就是会出现。研究的通讯作者Daria Peleg-Raibstein说：“目前为止大部分研究都只观察到第二代后代，或者只在第一代后代中观察肥胖和糖尿病的长期效应。本研究是第一个观察母亲过度进食对成瘾和肥胖的效应直至第三代后代的研究。”
作者们研究了这些影响，尤其是通过雄性后代传递的影响，直到第三代后代。他们的做法是，给雌性小鼠分别在交配前、孕期和哺乳期喂食高脂或正常饮食9周。她们的雄性后代随后再与经过标准喂食的雌性小鼠交配，生下第二代后代。第二代后代的雄性后代再次与标准饮食的雌性小鼠交配，产下第三代后代。
作者对第二代和第三代后代的体重、胰岛素敏感度、代谢率以及相关血液指标（如胰岛素和胆固醇水平）进行了测量。在行为实验中，他们研究了小鼠是否会更倾向于选择高脂饮食而非标准实验室饮食，或者更喜欢酒精溶液而非水，以及小鼠们在使用了安非他命（苯丙胺）之后的活动水平。他们这样做是为了更好的了解母系先辈的高脂肪饮食是否会影响后代的肥胖、过度进食和药物敏感度。
Peleg-Raibstein博士说：“为了对抗现在的肥胖流行病，了解其背后的机理、找到早期预防的方法非常重要。这个研究有助于改善孕期和哺乳期夫妇的健康咨询、教育，让他们的孩子、孙辈和曾孙辈更有可能以健康的方式生活。它提供了一种可能的方法帮人们找到肥胖和成瘾的高危因素，为高危人群提供早期干预的建议。”
Peleg-Raibstein博士补充说：“想将小鼠身上得到的结论用到人的身上，中间还有很大的距离，但是想在人类身上研究母亲过度饮食带来的影响几乎是不可能的，因为干扰因素太多，比如社会经济背景、父母的食物偏好或他们现在的健康状况。小鼠模型让我们可以在没有这些因素干扰的情况下，研究高脂饮食对后代的影响。”
还需要进一步的研究来确定女性高脂饮食的影响可能可以传递给后代的分子机理。
摘要：
Maternal overnutrition has been associated with increased susceptibility to develop obesity and neurological disorders later in life. Most epidemiological as well as experimental studies have focused on the metabolic consequences across generations following an early developmental nutritional insult. Recently, it has been shown that maternal high-fat diet (HFD) affects third-generation female body mass via the paternal lineage. We showed here that the offspring born to HFD ancestors displayed addictive-like behaviors as well as obesity and insulin resistance up to the third generation in the absence of any further exposure to HFD. These findings, implicate that the male germ line is a major player in transferring phenotypic traits. These behavioral and physiological alterations were paralleled by reduced striatal dopamine levels and increased dopamine 2 receptor density. Interestingly, by the third generation a clear gender segregation emerged, where females showed addictive-like behaviors while male HFD offspring showed an obesogenic phenotype. However, methylome profiling of F1 and F2 sperm revealed no significant difference between the offspring groups, suggesting that the sperm methylome might not be the major carrier for the transmission of the phenotypes observed in our mouse model. Together, our study for the first time demonstrates that maternal HFD insult causes sustained alterations of the mesolimbic dopaminergic system suggestive of a predisposition to develop obesity and addictive-like behaviors across multiple generations.
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期刊介绍:
Translational Psychiatry (, 2-year impact factor: 4.691, 5-year impact factor: 5.470) has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrods discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients.Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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