Direct calorimetry identifies deficiencies in respirometry for the determination of resting metabolic rate in C57Bl/6 and FVB mice

CML Burnett, JL Grobe - American Journal of Physiology …, 2013 - journals.physiology.org
CML Burnett, JL Grobe
American Journal of Physiology-Endocrinology And Metabolism, 2013journals.physiology.org
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 …
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.
American Physiological Society