Havel Peter J, Kievit Paul, Comuzzie Anthony G, Bremer Andrew A
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California.
Department of Nutrition, California National Primate Research Center, University of California, Davis, California.
ILAR J. 2017 Dec 1;58(2):251-268. doi: 10.1093/ilar/ilx031.
Obesity and its multiple metabolic sequelae, including type 2 diabetes, cardiovascular disease, and fatty liver disease, are becoming increasingly widespread in both the developed and developing world. There is an urgent need to identify new approaches for the prevention and treatment of these costly and prevalent metabolic conditions. Accomplishing this will require the use of appropriate animal models for preclinical and translational investigations in metabolic disease research. Although studies in rodent models are often useful for target/pathway identification and testing hypotheses, there are important differences in metabolic physiology between rodents and primates, and experimental findings in rodent models have often failed to be successfully translated into new, clinically useful therapeutic modalities in humans. Nonhuman primates represent a valuable and physiologically relevant model that serve as a critical translational bridge between basic studies performed in rodent models and clinical studies in humans. The purpose of this review is to evaluate the evidence, including a number of specific examples, in support of the use of nonhuman primate models in metabolic disease research, as well as some of the disadvantages and limitations involved in the use of nonhuman primates. The evidence taken as a whole indicates that nonhuman primates are and will remain an indispensable resource for evaluating the efficacy and safety of novel therapeutic strategies targeting clinically important metabolic diseases, including dyslipidemia and atherosclerosis, type 2 diabetes, hepatic steatosis, steatohepatitis, and hepatic fibrosis, and potentially the cognitive decline and dementia associated with metabolic dysfunction, prior to taking these therapies into clinical trials in humans.
肥胖及其多种代谢后遗症，包括2型糖尿病、心血管疾病和脂肪性肝病，在发达国家和发展中国家正变得越来越普遍。迫切需要确定预防和治疗这些代价高昂且普遍存在的代谢性疾病的新方法。要做到这一点，将需要在代谢疾病研究中使用适当的动物模型进行临床前和转化研究。尽管在啮齿动物模型中的研究通常有助于确定靶点/途径和检验假设，但啮齿动物和灵长类动物在代谢生理学上存在重要差异，并且啮齿动物模型中的实验结果往往未能成功转化为对人类新的、具有临床实用性的治疗方式。非人灵长类动物是一种有价值且与生理相关的模型，在啮齿动物模型中进行的基础研究和人类临床研究之间起着关键的转化桥梁作用。本综述的目的是评估支持在代谢疾病研究中使用非人灵长类动物模型的证据，包括一些具体例子，以及使用非人灵长类动物所涉及的一些缺点和局限性。总体而言，证据表明，在将针对临床上重要的代谢疾病（包括血脂异常和动脉粥样硬化、2型糖尿病、肝脂肪变性、脂肪性肝炎和肝纤维化，以及可能与代谢功能障碍相关的认知衰退和痴呆）的新型治疗策略用于人类临床试验之前，非人灵长类动物是且仍将是评估这些治疗策略疗效和安全性不可或缺的资源。
