Department of Pharmacology, Center on Functional Genomics of Hypertension, Fraternal Order of Eagles Diabetes Research Center, and The Obesity Research and Education Initiative, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa.
Am J Physiol Endocrinol Metab. 2013 Oct 1;305(7):E916-24. doi: 10.1152/ajpendo.00387.2013. Epub 2013 Aug 20.
Substantial research efforts have been aimed at identifying novel targets to increase resting metabolic rate (RMR) as an adjunct approach to the treatment of obesity. Respirometry (one form of "indirect calorimetry") is unquestionably the dominant technique used in the obesity research field to assess RMR in vivo, although this method relies upon a lengthy list of assumptions that are likely to be violated in pharmacologically or genetically manipulated animals. A "total" calorimeter, including a gradient layer direct calorimeter coupled to a conventional respirometer, was used to test the accuracy of respirometric-based estimations of RMR in laboratory mice (Mus musculus Linnaeus) of the C57Bl/6 and FVB background strains. Using this combined calorimeter, we determined that respirometry underestimates RMR of untreated 9- to 12-wk-old male mice by ∼10-12%. Quantitative and qualitative differences resulted between methods for untreated C57Bl/6 and FVB mice, C57Bl/6 mice treated with ketamine-xylazine anesthesia, and FVB mice with genetic deletion of the angiotensin II type 2 receptor. We conclude that respirometric methods underestimate RMR in mice in a magnitude that is similar to or greater than the desired RMR effects of novel therapeutics. Sole reliance upon respirometry to assess RMR in mice may lead to false quantitative and qualitative conclusions regarding the effects of novel interventions. Increased use of direct calorimetry for the assessment of RMR and confirmation of respirometry results and the reexamination of previously discarded potential obesity therapeutics are warranted.
大量的研究工作旨在寻找新的靶点来提高静息代谢率（RMR），作为治疗肥胖症的辅助方法。呼吸测量法（“间接测热法”的一种形式）无疑是肥胖症研究领域中用于评估体内 RMR 的主要技术，尽管这种方法依赖于一长串可能在药理学或基因操作动物中被违反的假设。使用包括与传统呼吸计耦合的梯度层直接测热计的“总”量热计，我们测试了基于呼吸计的 RMR 估计在 C57Bl/6 和 FVB 背景品系的实验室小鼠（Mus musculus Linnaeus）中的准确性。使用这种组合量热计，我们确定呼吸计低估了未经处理的 9 至 12 周龄雄性小鼠的 RMR，低估了约 10-12%。未经处理的 C57Bl/6 和 FVB 小鼠、用氯胺酮-甲苯噻嗪麻醉处理的 C57Bl/6 小鼠以及基因缺失血管紧张素 II 型 2 受体的 FVB 小鼠之间的方法存在定量和定性差异。我们得出结论，呼吸计方法低估了小鼠的 RMR，其幅度与新型治疗剂的预期 RMR 效果相似或更大。仅依靠呼吸计来评估小鼠的 RMR 可能会导致关于新型干预措施效果的错误的定量和定性结论。增加直接测热法评估 RMR 和确认呼吸计结果，并重新检查以前被丢弃的潜在肥胖治疗药物，这是必要的。
