Kaiyala’s impression that we compared VO2 between obese Trpv1 knockout mice and lean wild-type controls is erroneous. All thermoregulation-related measurements in our study were made in young (~17 weeks) mice of similar (~30 g) body mass. Therefore, dividing VO2 by body mass was correct and led to sound conclusions. No reanalysis is needed. With age, Trpv1 knockout mice develop obesity, but we did not study VO2 in old, ob...
Kaiyala’s impression that we compared VO2 between obese Trpv1 knockout mice and lean wild-type controls is erroneous. All thermoregulation-related measurements in our study were made in young (~17 weeks) mice of similar (~30 g) body mass. Therefore, dividing VO2 by body mass was correct and led to sound conclusions. No reanalysis is needed. With age, Trpv1 knockout mice develop obesity, but we did not study VO2 in old, obese mice. Even though Kaiyala’s point is irrelevant to our study design and has no effect on our conclusions, it attracted our attention to his recent papers, which we read with interest.
Garami et al. report that Trpv 1 knockout mice have a "hypometabolic" phenotype but do so based on having normalized metabolic rate (VO2) by dividing whole-animal VO2 values by body mass.
It is well established (but not yet widely understood among mouse researchers) that this traditional ratio method is seriously confounded by differences in body mass such that heavier mice are essentially preordained to exhibi...
Garami et al. report that Trpv 1 knockout mice have a "hypometabolic" phenotype but do so based on having normalized metabolic rate (VO2) by dividing whole-animal VO2 values by body mass.
It is well established (but not yet widely understood among mouse researchers) that this traditional ratio method is seriously confounded by differences in body mass such that heavier mice are essentially preordained to exhibit lower normalized metabolic rates than lighter mice. Moreover, this problem persists even when metabolic rate is divided by measures of "metabolic body size" (lean body mass or fat free mass).
Given that Trpv 1 knockout mice exhibit a heavier phenotype than wildtype controls, we urge the authors to reanalyze their metabolic rate data using analysis of covariance.
We are attempting to alert investigators who use mice and other animal models to the serious problem of traditional ratio normalization of metabolic rate.
1. Kaiyala KJ, Morton GJ, Leroux BG, Ogimoto K, Wisse B, Schwartz MW: Identification of body fat mass as a major determinant of metabolic rate in mice. Diabetes 59:1657-1666, 2010
2. Kaiyala KJ, Schwartz MW: Toward a more complete (and less controversial) understanding of energy expenditure and its role in obesity pathogenesis. Diabetes 60:17-23, 2011
We have no competing interests.