Whelan J, Whelan Jay
Department of Nutrition, 1215 West Cumberland Avenue, 229 Jessie Harris Building, University of Tennessee, Knoxville, TN 37996-1920 USA; Tennessee Agricultural Experiment Station, University of Tennessee Institute of Agriculture, University of Tennessee, Knoxville, TN 37996 USA.
Professor, Head, Department of Nutrition, Interim Head, Department of Public Health, 1215 West Cumberland Avenue, 229 Jessie Harris Building, University of Tennessee, Knoxville, TN 37996-1920, USA.
Prostaglandins Leukot Essent Fatty Acids. 2020 Jul;158:102094. doi: 10.1016/j.plefa.2020.102094. Epub 2020 May 15.
The purpose of this research was to explore various allometric scaling models for dietary nutrients to improve translational validity between preclinical experimental rodent models and humans, focusing on polyunsaturated fats. Currently, there is no authoritative document that provides standardized guidelines for which dietary designs can be based on to improve translational fidelity between species. This paper reviews the challenges of using a rodent model, the major allometric scaling models, the use of these mathematical models to extrapolate human equivalent doses, and then tests one of these models using data generated in mice, with comparisons of data generated in human clinical trials. Mice were fed diets containing micro- and macronutrient compositions that approximated the US diet based on energy distribution and were then supplemented with increasing levels of various n-3 and n-6 polyunsaturated fatty acids at human equivalent doses. Changes in plasma and erythrocyte fatty acid phospholipid compositions were determined and compared to corresponding data generated in humans. Our findings suggest that basing lipid composition on percent of energy may result in comparable outcomes between mice and humans and that extrapolation of non-energy producing nutrients between species might be done using differences in energy needs (based on food intake).
本研究的目的是探索膳食营养素的各种异速生长比例模型，以提高临床前实验啮齿动物模型与人类之间的转化效度，重点关注多不饱和脂肪。目前，尚无权威文件提供标准化指南，以确定可依据哪些膳食设计来提高物种间的转化保真度。本文回顾了使用啮齿动物模型的挑战、主要的异速生长比例模型、使用这些数学模型推断人类等效剂量的情况，然后使用小鼠产生的数据对其中一个模型进行测试，并与人类临床试验产生的数据进行比较。给小鼠喂食含有基于能量分布近似美国饮食的微量和常量营养素组成的饲料，然后以人类等效剂量补充不同水平的各种n-3和n-6多不饱和脂肪酸。测定血浆和红细胞脂肪酸磷脂组成的变化，并与人类产生的相应数据进行比较。我们的研究结果表明，基于能量百分比的脂质组成可能会导致小鼠和人类之间产生可比的结果，并且物种间非能量产生营养素的推断可能可以利用能量需求差异（基于食物摄入量）来进行。
