Miniature-pig models for human metabolic disorders such as obesity and metabolic syndrome are gaining popularity. However, in-depth knowledge on the phenotypic and metabolic effects of metabolic dysregulation is lacking, and ad libitum feeding is not well-characterized in these pig breeds. Therefore, an investigation was performed into the metabolome of Yucatan minipigs fed ad libitum or restricted diets. Furthermore, we used cloned and conventional minipigs to assess if cloning reflects a presumably lowered variation between subjects. For 5 months, 17 female Yucatan minipigs were fed either ad libitum or restricted Western-style diets. Serum, urine, and liver tissues were collected and analyzed by non-targeted liquid chromatography-mass spectrometry metabolomics and by biochemical analyses. Several metabolic pathways were deregulated as a result of obesity and increased energy-dense feed intake, particularly the hepatic glutathione pathway and the pantothenic acid and tryptophan metabolic pathways in serum and urine. Although cloned minipigs were phenotypically similar to wild-type minipigs, the metabolomics analysis of serum and liver tissues showed several altered pathways, such as amino acid and purine metabolism. These changes, as an effect of cloning, could limit the use of cloned models in dietary intervention studies and provides no evidence of decreased variability between subjects.

中文翻译：

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微型尤卡坦猪模型中的肥胖症发展：限制和自由采食高能饮食的克隆猪和正常猪的多室代谢组学研究。

用于人类代谢性疾病（例如肥胖症和代谢综合征）的小型猪模型越来越受欢迎。然而，缺乏对代谢失调的表型和代谢作用的深入了解，而且在这些猪品种中随意采食的特征还不充分。因此，对随意喂养或限制饮食的尤卡坦小型猪的代谢组进行了研究。此外，我们使用克隆的和常规的迷你猪来评估克隆是否反映出受试者之间变异的降低。为期5个月，自由采食或限制西式饮食喂养了17头雌性尤卡坦小型猪。收集血清，尿液和肝组织，并通过非靶向液相色谱-质谱代谢组学和生化分析进行分析。肥胖和增加能量密集饲料的摄入量导致几种代谢途径被放松，特别是血清和尿液中的肝谷胱甘肽途径以及泛酸和色氨酸代谢途径。尽管克隆的小型猪在表型上与野生型小型猪相似，但是对血清和肝组织的代谢组学分析显示出几种改变的途径，例如氨基酸和嘌呤代谢。作为克隆的影响，这些变化可能会限制在饮食干预研究中使用克隆的模型，并且无法提供受试者之间变异性降低的证据。尽管克隆的小型猪在表型上与野生型小型猪相似，但是对血清和肝脏组织的代谢组学分析显示出几种改变的途径，例如氨基酸和嘌呤代谢。作为克隆的影响，这些变化可能会限制在饮食干预研究中使用克隆的模型，并且无法提供受试者之间变异性降低的证据。尽管克隆的小型猪在表型上与野生型小型猪相似，但是对血清和肝脏组织的代谢组学分析显示出几种改变的途径，例如氨基酸和嘌呤代谢。作为克隆的影响，这些变化可能会限制在饮食干预研究中使用克隆的模型，并且无法提供受试者之间变异性降低的证据。