Estimating energy expenditure in mice using an energy balance technique (original) (raw)
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Measuring energy metabolism in the mouse – theoretical, practical, and analytical considerations
The mouse is one of the most important model organisms for understanding human genetic function and disease. This includes characterization of the factors that influence energy expenditure and dysregulation of energy balance leading to obesity and its sequelae. Measuring energy metabolism in the mouse presents a challenge because the animals are small, and in this respect it presents similar challenges to measuring energy demands in many other species of small mammal.This paper considers some theoretical, practical, and analytical considerations to be considered when measuring energy expenditure in mice. Theoretically total daily energy expenditure is comprised of several different components: basal or resting expenditure, physical activity, thermoregulation, and the thermic effect of food. Energy expenditure in mice is normally measured using open flow indirect calorimetry apparatus. Two types of system are available -one of which involves a single small Spartan chamber linked to a single analyzer, which is ideal for measuring the individual components of energy demand. The other type of system involves a large chamber which mimics the home cage environment and is generally configured with several chambers/analyzer. These latter systems are ideal for measuring total daily energy expenditure but at present do not allow accurate decomposition of the total expenditure into its components. The greatest analytical challenge for mouse expenditure data is how to account for body size differences between individuals. This has been a matter of some discussion for at least 120 years. The statistically most appropriate approach is to use analysis of covariance with individual aspects of body composition as independent predictors.
A guide to analysis of mouse energy metabolism
Nature Methods, 2012
We present a consolidated view of the complexity and challenges of designing studies for measurement of energy metabolism in mouse models, including a practical guide to the assessment of energy expenditure, energy intake and body composition and statistical analysis thereof. We hope this guide will facilitate comparisons across studies and minimize spurious interpretations of data. We recommend that division of energy expenditure data by either body weight or lean body weight and that presentation of group effects as histograms should be replaced by plotting individual data and analyzing both group and body-composition effects using analysis of covariance (ANCOVA).
METHODOLOGICAL EVALUATION OF INDIRECT CALORIMETRY DATA IN LEAN AND OBESE RATS
Clinical and Experimental Pharmacology and Physiology, 1993
1. The applicability of current indirect calorimetry formulae to the study of energy and substrate balances on obese rats has been evaluated. The energy consumption of series of 60-day rats of Wistar, lean and obese Zucker stock were studied by means of direct and indirect calorimetry, and by establishing their energy balance through measurement of food intake and retention. Calorimetric studies encompassed a 24 h period, with gas and heat output measurements every 2 or 5 min, respectively, for direct and indirect calorimetry. 2. The analysis of fat composition (diet, whole rat, and synthesized and oxidized fat) showed only small variations that had only a limited effect on the overall energy equation parameters. 3. A gap in the nitrogen balance, which represents a urinary N excretion lower than the actual protein oxidized, resulted in significant deviations in the estimation of carbohydrate and lipid oxidized when using the equations currently available for indirect calorimetry. 4. Analysis of the amino acid composition of diet and rat protein as well as of the portion actually oxidized, and correcting for the nitrogen gap allowed the establishment of a set of equations that gave better coincidence of the calculated data with the measured substrate balance. 5. The measured heat output of all rats was lower than the estimated values calculated by means of either indirect calorimetry of direct energy balance measurement; the difference corresponded to the energy lost in water evaporation, and was in the range of one-fifth of total energy produced in the three rat stocks. 6. Wistar rats showed a biphasic circadian rhythm of substrate utilization, with alternate lipid synthesis/degradation that reversed that of carbohydrate, concordant with nocturnal feeding habits. Zucker rats did not show this rhythm; obese rats synthesized large amounts of fat during most of the light period, consuming fat at the end of the dark period, which suggests more diurnal feeding habits. Lean Zucker rats showed a similar, but less marked pattern. 7. The results obtained indicate that lean and obese rats can be studied using the same indirect calorimetry formulae provided that there is an adequate measure of protein oxidation and the composition of diet does not differ.
Integration of body temperature into the analysis of energy expenditure in the mouse
Molecular Metabolism, 2015
Objectives: We quantified the effect of environmental temperature on mouse energy homeostasis and body temperature. Methods: The effect of environmental temperature (4e33 C) on body temperature, energy expenditure, physical activity, and food intake in various mice (chow diet, high-fat diet, Brs3-/y , lipodystrophic) was measured using continuous monitoring. Results: Body temperature depended most on circadian phase and physical activity, but also on environmental temperature. The amounts of energy expenditure due to basal metabolic rate (calculated via a novel method), thermic effect of food, physical activity, and cold-induced thermogenesis were determined as a function of environmental temperature. The measured resting defended body temperature matched that calculated from the energy expenditure using Fourier's law of heat conduction. Mice defended a higher body temperature during physical activity. The cost of the warmer body temperature during the active phase is 4e16% of total daily energy expenditure. Parameters measured in diet-induced obese and Brs3-/y mice were similar to controls. The high post-mortem heat conductance demonstrates that most insulation in mice is via physiological mechanisms. Conclusions: At 22 C, cold-induced thermogenesis is w120% of basal metabolic rate. The higher body temperature during physical activity is due to a higher set point, not simply increased heat generation during exercise. Most insulation in mice is via physiological mechanisms, with little from fur or fat. Our analysis suggests that the definition of the upper limit of the thermoneutral zone should be reconsidered. Measuring body temperature informs interpretation of energy expenditure data and improves the predictiveness and utility of the mouse to model human energy homeostasis.
The Journal of nutrition, 1980
Maintenance energy requirements were estimated for female obese (ob/ob) and lean littermates housed at 33°.Mice were weaned at 21 days of age and fed either a high-carbohydrate or a high-fat diet at three levels of intake for 21 days. Linear regressions relating changes in total body energy to metabolizable-energy intake were used to estimate maintenance energy requirements. To maintain body energy at 33°,obese and lean mice required approximately 72 and 92 kcal per kg3/* per day, respectively. (One kilocalorie equals 4.184 kilojoules.) Diet did not sig nificantly affect maintenance energy requirements. Lean mice fed either diet and obese mice fed the high-carbohydrate diet retained 61% of the metabolizable energy consumed above the maintenance requirement. But obese mice fed the high-fat diet were more efficient; they retained 81% of the metabolizable energy consumed above maintenance. Lean mice deposited a greater percentage of the metabolizable energy available for gain as protein than did obese mice. As expected, maintenance require ments of lean mice housed at 33°were reduced (approximately 25%) compared with results from an earlier study conducted at 25 to 30°.But maintenance energy requirements of obese mice were not changed when the environmental temperature was increased to 33°.Even though obese mice were more efficient in retaining dietary energy than were lean mice at both temperatures examined, the differences were greater at 25 to 30°t han at 33°.
1979
Maintenance energy requirements were estimated for female obese (ob/ob) and lean littermates housed at 33°.Mice were weaned at 21 days of age and fed either a high-carbohydrate or a high-fat diet at three levels of intake for 21 days. Linear regressions relating changes in total body energy to metabolizable-energy intake were used to estimate maintenance energy requirements. To maintain body energy at 33°,obese and lean mice required approximately 72 and 92 kcal per kg3/* per day, respectively. (One kilocalorie equals 4.184 kilojoules.) Diet did not sig nificantly affect maintenance energy requirements. Lean mice fed either diet and obese mice fed the high-carbohydrate diet retained 61% of the metabolizable energy consumed above the maintenance requirement. But obese mice fed the high-fat diet were more efficient; they retained 81% of the metabolizable energy consumed above maintenance. Lean mice deposited a greater percentage of the metabolizable energy available for gain as protein than did obese mice. As expected, maintenance require ments of lean mice housed at 33°were reduced (approximately 25%) compared with results from an earlier study conducted at 25 to 30°.But maintenance energy requirements of obese mice were not changed when the environmental temperature was increased to 33°.Even though obese mice were more efficient in retaining dietary energy than were lean mice at both temperatures examined, the differences were greater at 25 to 30°t han at 33°.
Molecular metabolism, 2014
Inference in science depends on us having the right tools to measure with sufficient accuracy and precision the phenomena we are attempting to understand. In this issue of Molecular Metabolism, Burnett and Grobe call into question the accuracy of respirometry, the standard method for measuring energy expenditure in animals and humans . This is an important contribution because in the field of obesity, almost without exception, scientists are agreed that the problem is due to energy imbalance. Energy intake is too high, expenditure is too low, or both. This energy balance framework provides a useful starting point for any discussions about fat storage and obesity . However, the level of energy imbalance that can drive fat storage is rather small. An example is given in Ref.
Mechanisms of Ageing and Development, 2005
Debate exists over the impact of caloric restriction (CR) on the level of energy expenditure. At the whole animal level, CR decreases metabolic rates but in parallel body mass also declines. The question arises whether the reduction in metabolism is greater, smaller or not different from the expectation based on body mass change alone. Answers to this question depend on how metabolic rate is normalized and it has recently been suggested that this issue can only be resolved through detailed morphological investigation. Added to this issue is the problem of how appropriate the resting energy expenditure is to characterize metabolic events relating to aging phenomena. We measured the daily energy demands of young and old rats under ad libitum (AD) food intake or 40% CR, using the doubly labeled water (DLW) method and made detailed morphological examination of individuals, including 21 different body components. Whole body energy demands of CR rats were lower than AD rats, but the extent of this difference was much less than expected from the degree of caloric restriction, consistent with other studies using the DLW method on CR animals. Using multiple regression and multivariate data reduction methods we built two empirical predictive models of the association between daily energy demands and body composition using the ad lib animals. We then predicted the expected energy expenditures of the CR animals based on their altered morphology and compared these predictions to the observed daily energy demands. Independent of how we constructed the prediction, young and old rats under CR expended 30 and 50% more energy, respectively, than the prediction from their altered body composition. This effect is consistent with recent intra-specific observations of positive associations between energy metabolism and lifespan and theoretical ideas about mechanisms underpinning the relationship between oxygen consumption and reactive oxygen species production in mitochondria. #
Journal of Nutrition
Female obese (ob/ob) and lean mice were weaned at 21 days of age, placed in wire-mesh cages maintained at 25 to 30 degrees, and fed a high-fat or a high-carbohydrate diet for 21 days. The body energy balance procedure was utilized to determine the maintenance energy requirements, and the efficiency of dietary energy utilization, above maintenance, in these mice. Heat production of each mouse was measured weekly in a gradient-layer calorimeter. Regressions of changes in body energy per kg3/4 on metabolizable energy intake per kg3/4 indicated that the maintenance energy requirement averaged 72 kcal/kg3/4/day for obese mice and 124 kcal/kg3/4/day for lean mice. Diet composition did not influence the maintenance energy requirements, but utilization of energy, above maintenance, in obese mice fed the high-fat diet was 41% more efficient than observed in obese mice fed the high-carbohydrate diet and 38 to 71% more efficient than observed in lean mice. Heat production, per unit body weight...
Progress and challenges in analyzing rodent energy expenditure
Nature Methods, 2019
Whole-body energy expenditure is the summed metabolic activities of tissues and, to remove the influence of body size, ratios of energy expenditure to body mass are often applied but can generate spurious differences. In 2011, a group of experts proposed adoption of ANCOVA for the analysis of metabolic rate but, seven years later, analyses based on ratios remain the most frequent. We discuss some of the barriers to adopting better analytical procedures.