Laboratory of Integrative and Systems Physiology, École Polytchnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Cell Syst. 2018 Jun 27;6(6):709-721.e6. doi: 10.1016/j.cels.2018.05.009. Epub 2018 Jun 13.
The genetic regulation and physiological impact of most lipid species are unexplored. Here, we profiled 129 plasma lipid species across 49 strains of the BXD mouse genetic reference population fed either chow or a high-fat diet. By integrating these data with genomics and phenomics datasets, we elucidated genes by environment (diet) interactions that regulate systemic metabolism. We found quantitative trait loci (QTLs) for ∼94% of the lipids measured. Several QTLs harbored genes associated with blood lipid levels and abnormal lipid metabolism in human genome-wide association studies. Lipid species from different classes provided signatures of metabolic health, including seven plasma triglyceride species that associated with either healthy or fatty liver. This observation was further validated in an independent mouse model of non-alcoholic fatty liver disease (NAFLD) and in plasma from NAFLD patients. This work provides a resource to identify plausible genes regulating the measured lipid species and their association with metabolic traits.
大多数脂质种类的遗传调控和生理影响仍未被探索。在这里，我们对 49 个 BXD 小鼠遗传参考群体的 129 种血浆脂质种类进行了分析，这些小鼠分别喂食标准饮食或高脂肪饮食。通过将这些数据与基因组学和表型数据集整合，我们阐明了调节系统代谢的基因与环境（饮食）相互作用。我们发现了约 94%所测量脂质的数量性状基因座 (QTL)。一些 QTL 携带与人类全基因组关联研究中的血脂水平和异常脂质代谢相关的基因。不同类别脂质种类提供了代谢健康的特征，包括七种与健康或脂肪肝相关的血浆甘油三酯种类。这一观察结果在非酒精性脂肪性肝病 (NAFLD) 的另一个独立小鼠模型和 NAFLD 患者的血浆中得到了进一步验证。这项工作提供了一个资源，以识别可能调节所测量脂质种类及其与代谢特征相关的基因。
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