Metabolic diseases are a host of complex conditions, including obesity, diabetes mellitus, and metabolic syndrome. Endocrine control systems (eg, adrenals, thyroid, gonads) are causally linked to metabolic health outcomes. N/NIH Heterogeneous Stock (HS) rats are a genetically heterogeneous outbred population developed for genetic studies of complex traits. Genetic mapping studies in adult HS rats identified loci associated with cardiometabolic risks, such as glucose intolerance, insulin resistance, and increased body mass index. This study determined underappreciated metabolic health traits and the associated endocrine glands within available substrains of the HS rat founders. We hypothesize that the genetic diversity of the HS rat founder strains causes a range of endocrine health conditions contributing to the diversity of cardiometabolic disease risks. ACI/EurMcwi, BN/NHsdMcwi, BUF/MnaMcwi, F344/StmMcwi, M520/NRrrcMcwi, and WKY/NCrl rats of both sexes were studied from birth until 13 weeks of age. Birth weight was recorded, body weight was measured weekly, metabolic characteristics were assessed, and blood and tissues were collected. Our data show wide variation in endocrine traits and metabolic health states in ACI, BN, BUF, F344, M520, and WKY rat strains. This is the first report to compare birth weight, resting metabolic rate, endocrine gland weight, hypothalamic-pituitary-thyroid axis hormones, and brown adipose tissue weight in these rat strains. Importantly, this work unveils new potential for the HS rat population to model early life adversity and adrenal and thyroid pathophysiology. The HS population likely inherited risk alleles for these strain-specific traits, making the HS rat a powerful model to investigate interventions on endocrine and metabolic health.

中文翻译：

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异质种鼠创始人品系在代谢疾病建模中的作用。

代谢疾病是一系列复杂的疾病，包括肥胖、糖尿病和代谢综合征。内分泌控制系统（例如肾上腺、甲状腺、性腺）与代谢健康结果存在因果关系。N/NIH 异质种 (HS) 大鼠是一种遗传异质的远交群体，专为复杂性状的遗传研究而开发。对成年 HS 大鼠进行的基因图谱研究发现了与心脏代谢风险相关的位点，例如葡萄糖不耐受、胰岛素抵抗和体重指数增加。这项研究确定了 HS 大鼠现有亚系中未被充分认识的代谢健康特征和相关内分泌腺。我们假设 HS 大鼠品系的遗传多样性会导致一系列内分泌健康状况，从而导致心脏代谢疾病风险的多样性。对两种性别的 ACI/EurMcwi、BN/NHsdMcwi、BUF/MnaMcwi、F344/StmMcwi、M520/NRrrcMcwi 和 WKY/NCrl 大鼠从出生到 13 周龄进行研究。记录出生体重，每周测量体重，评估代谢特征，并收集血液和组织。我们的数据显示 ACI、BN、BUF、F344、M520 和 WKY 大鼠品系的内分泌特征和代谢健康状态存在很大差异。这是第一份比较这些大鼠品系的出生体重、静息代谢率、内分泌腺重量、下丘脑-垂体-甲状腺轴激素和棕色脂肪组织重量的报告。重要的是，这项工作揭示了 HS 大鼠群体模拟早期生活逆境以及肾上腺和甲状腺病理生理学的新潜力。HS 群体可能遗传了这些品系特异性特征的风险等位基因，使 HS 大鼠成为研究内分泌和代谢健康干预措施的强大模型。