An RNA-seq atlas of mouse brain areas during fasting and diet-induced obesity

Mammalian energy homeostasis is regulated by the hypothalamus and hindbrain, with the hippocampus, midbrain nuclei, and other regions implicated by evidence from human genetics studies. In order to understand how these brain regions respond to imbalances in energy homeostasis, we performed two experiments examining the effects of different diets in male C57BL6 mice. In our first study, groups of 6 pair-housed mice were given access to chow, high-fat diet or fasted for 16 hours. In our subsequent study, two groups of 10 mice were single-housed and given access to chow or fasted for 24h. We recorded food intake for each cage, the change in body weight for each animal, and collected hypothalamus, hippocampus, superior colliculus, inferior colliculus, prefrontal cortex, and zona incerta samples. We performed bulk RNA sequencing on 185 samples and validated them by a series of quality control assessments including alignment quality and gene expression profiling. We believe these studies capture the transcriptomic effects of acute fasting and high fat diet in the rodent brain and provide a valuable reference. In the 16-hour study, 6 animals per group were pair housed and either fasted, kept on a chow diet, or switched to a HFD for 16 hours before being sacrificed. Hypothalamus, hippocampus, superior colliculus, inferior colliculus, and prefrontal cortex from each animal were sequenced In the 24-hour study, 9 animals were kept on a chow diet and 10 animals were fasted. All animals were single housed and acclimatized for three days before the start of the experiment. After 24 hours of their respective diets, animals were sacrificed and the hypothalamus, hippocampus, superior colliculus, inferior colliculus, and zona incerta were sequenced哺乳动物能量稳态由下丘脑（hypothalamus）与后脑调控，现有人类遗传学研究证据提示海马体（hippocampus）、中脑核团等脑区亦参与其中。为阐明上述脑区如何响应能量稳态失衡，我们以雄性C57BL/6小鼠为模型开展两项实验，探究不同膳食干预的影响。在第一项研究中，每组6只成对饲养的小鼠分别给予普通饲料、高脂膳食（high-fat diet, HFD）或进行16小时禁食处理。在后续研究中，两组各10只单笼饲养的小鼠分别给予普通饲料或进行24小时禁食。我们记录了每笼小鼠的进食量、每只小鼠的体重变化，并采集了下丘脑、海马体、上丘（superior colliculus）、下丘（inferior colliculus）、前额叶皮层（prefrontal cortex）以及未定带（zona incerta）的组织样本。我们对185份样本开展批量RNA测序（bulk RNA sequencing），并通过比对质量评估、基因表达谱分析等一系列质量控制流程对测序数据进行验证。本研究认为，上述两项实验阐明了急性禁食与高脂膳食对啮齿类动物脑内的转录组学影响，可为相关领域提供极具价值的参考数据集。在16小时干预实验中，每组6只成对饲养的小鼠分别接受16小时禁食、普通饲料喂养，或切换至高脂膳食喂养16小时后实施安乐处死，采集每只小鼠的下丘脑、海马体、上丘、下丘及前额叶皮层组织进行测序。在24小时干预实验中，9只小鼠维持普通饲料喂养，10只小鼠接受禁食处理；所有小鼠均采用单笼饲养，并在实验开始前适应环境3天。在接受对应膳食干预24小时后，对小鼠实施安乐处死，并采集下丘脑、海马体、上丘、下丘及未定带组织进行测序。