Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45, Gothenburg, Sweden.
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000, Lille, France.
Mol Metab. 2019 May;23:82-87. doi: 10.1016/j.molmet.2019.02.010. Epub 2019 Mar 9.
The nuclear receptor superfamily is a potential target for the development of new treatments for obesity and metabolic diseases. Increasing evidence has pointed towards the retinoic acid-related orphan receptor-alpha (RORα) as an important nuclear receptor involved in several biological processes. RORα full body knockout mice display improved metabolic phenotypes on both chow and high fat (60% fat, 20% carbohydrate) diets, but also have severe behavioral abnormalities. Here we investigated the effect of hepatic RORα by generating mice with liver-specific RORα deletion to elucidate the role of this nuclear receptor on host metabolism.
8 week-old mice with liver-specific RORα deletion and littermate controls were fed either chow or western-style diets (40% fat, 40% carbohydrate) for 12 weeks. Metabolic phenotyping was performed at the end of the dietary intervention.
Here, we show that hepatic RORα deletion does not affect the metabolic susceptibility to either chow or western-style diet in terms of glucose metabolism and adiposity.
Our data indicate that liver deletion of RORα does not have a pivotal role in the regulation of hepatic glucose and lipid metabolism on chow or western-style diet.
核受体超家族是开发肥胖和代谢性疾病新疗法的潜在靶点。越来越多的证据表明，维甲酸相关孤儿受体-α（RORα）是参与多种生物学过程的重要核受体。RORα 全身敲除小鼠在标准饲料和高脂肪（60%脂肪，20%碳水化合物）饮食中表现出改善的代谢表型，但也有严重的行为异常。在这里，我们通过生成肝脏特异性 RORα 缺失的小鼠来研究肝脏 RORα 的作用，以阐明该核受体对宿主代谢的作用。
8 周龄的肝脏特异性 RORα 缺失小鼠及其同窝对照小鼠分别喂食标准饲料或西式饮食（40%脂肪，40%碳水化合物）12 周。在饮食干预结束时进行代谢表型分析。
我们发现，肝脏 RORα 缺失不会影响葡萄糖代谢和肥胖程度对标准饲料或西式饮食的代谢易感性。
我们的数据表明，肝脏 RORα 的缺失在调节标准饲料或西式饮食中的肝脏葡萄糖和脂质代谢方面没有关键作用。
