CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, 1150-082 Lisboa, Portugal.
Instituto de Investigação Clínica e Biomédica de Coimbra (iCBR), Faculdade de Medicina de Coimbra, 3000-548 Coimbra, Portugal.
Nutrients. 2019 May 28;11(6):1197. doi: 10.3390/nu11061197.
Animal experimentation has a long history in the study of metabolic syndrome-related disorders. However, no consensus exists on the best models to study these syndromes. Knowing that different diets can precipitate different metabolic disease phenotypes, herein we characterized several hypercaloric rat models of obesity and type 2 diabetes, comparing each with a genetic model, with the aim of identifying the most appropriate model of metabolic disease. The effect of hypercaloric diets (high fat (HF), high sucrose (HSu), high fat plus high sucrose (HFHSu) and high fat plus streptozotocin (HF+STZ) during different exposure times (HF 3 weeks, HF 19 weeks, HSu 4 weeks, HSu 16 weeks, HFHSu 25 weeks, HF3 weeks + STZ) were compared with the Zucker fatty rat. Each model was evaluated for weight gain, fat mass, fasting plasma glucose, insulin and C-peptide, insulin sensitivity, glucose tolerance, lipid profile and liver lipid deposition, blood pressure, and autonomic nervous system function. All animal models presented with insulin resistance and dyslipidemia except the HF+STZ and HSu 4 weeks, which argues against the use of these models as metabolic syndrome models. Of the remaining animal models, a higher weight gain was exhibited by the Zucker fatty rat and wild type rats submitted to a HF diet for 19 weeks. We conclude that the latter model presents a phenotype most consistent with that observed in humans with metabolic disease, exhibiting the majority of the phenotypic features and comorbidities associated with type 2 diabetes in humans.
动物实验在代谢综合征相关疾病的研究中有着悠久的历史。然而，对于研究这些综合征的最佳模型，尚未达成共识。鉴于不同的饮食可以引发不同的代谢疾病表型，在此我们描述了几种肥胖和 2 型糖尿病的高热量大鼠模型，将每种模型与一种遗传模型进行比较，旨在确定最合适的代谢疾病模型。高热量饮食（高脂肪（HF）、高蔗糖（HSu）、高脂肪加高蔗糖（HFHSu）和高脂肪加链脲佐菌素（HF+STZ））在不同暴露时间（HF 3 周、HF 19 周、HSu 4 周、HSu 16 周、HFHSu 25 周、HF3 周+STZ）下的作用与 Zucker 肥胖大鼠进行了比较。每种模型均评估了体重增加、脂肪量、空腹血糖、胰岛素和 C 肽、胰岛素敏感性、葡萄糖耐量、血脂谱和肝脏脂质沉积、血压和自主神经系统功能。除了 HF+STZ 和 HSu 4 周外，所有动物模型均表现出胰岛素抵抗和血脂异常，这表明这些模型不适合作为代谢综合征模型。在其余的动物模型中，Zucker 肥胖大鼠和接受 HF 饮食 19 周的野生型大鼠体重增加更多。我们得出结论，后一种模型表现出与人类代谢疾病最一致的表型，表现出大多数与人类 2 型糖尿病相关的表型特征和合并症。
