RenaSci

Energy Expenditure

TSE PhenoMaster Indirect Calorimetry System

 

Body weight is a balance between energy input (food intake) and energy output (comprising resting metabolic rate, meal-induced thermogenesis and physical activity). Weight-loss can be produced by drugs that reduce food intake and/or increase energy expenditure. The mechanisms underlying the reduction in body weight produced by novel antiobesity drugs should always be investigated by measuring the effects of the compound on both sides of the energy equation balance. 


RenaSci offer a fully comprehensive metabolic profiling service using the TSE PhenoMaster System. The equipment uses indirect calorimetry to determine the effects of drugs on energy expenditure and allows simultaneous and automated measurement of the following parameters in rats or mice

 

  • Oxygen consumption (VO2)
  • Carbon dioxide production (VCO2)
  • Energy expenditure (derived from VO2 and VCO2)
  • Respiratory exchange ratio (RER; which estimates relative substrate utilization, ie shifts in fat and carbohydrate utilization)
  • Food and water intake
  • Meal and drink patterns (ie frequency and size)
  • Physical activity (measured as beam breaks on the x, y and z axis)

 

The TSE indirect calorimetry system has 16 cages. Standard individually ventilated cages are used to resemble the home cage. Readings are provided for each cage every 20 min for up to 5 days. Data can be calculated over various time-points eg hourly, daily or to determine photoperiod-specific effects. The response to fasting and re-feeding can be assessed and also the effects of drugs on food preferences.

 

Assessment of the metabolic phenotype in the TSE PhenoMaster can be performed as part of a chronic study or as a standalone acute study. 


We have validated the TSE PhenoMaster by using it to assess the effects of the β3-adrenergic receptor agonist, CL-316,243, on energy expenditure and energy input in dietary-induced obese mice. Body weight was also measured. This drug was used as a reference compound as its ability to stimulate energy expenditure in animals has been well-established.

 

CL-316,243 Reduces Body Weight in DIO Mice

 CL-316,243 Increases Energy Expenditure in DIO Mice

 

CL-316,243 Increases Utilization of Fat (Reduces RER) in DIO Mice

 

The Effect of CL-316,243 on Physical Activity in DIO Mice

 

CL-316,243 produced weight-loss which was associated with an increase in energy expenditure. The increase in energy expenditure was independent of changes in physical activity or meal-induced thermogenesis. The rapid reduction in the respiratory exchange ratio (RER) indicates an increased utilization of fat.

 

CL-316,243 also reduced food intake.

 

CL-316,243 Reduces Food Intake in DIO Rats

 

The decrease in food intake produced by CL-316,243 in the dietary-induced obese mice was associated with a reduction in the number of meals and meal size. These effects were particularly evident during Day 1.


CL-316,243 Reduces the Number and Size of Meals in DIO Mice

 

The results demonstrate that metabolic profiling by the TSE PhenoMaster is a useful tool for gaining insight into the mode of action of novel antiobesity drugs.

We have also validated the TSE PhenoMaster system using CL-316,243 in rats fed a high fat diet.

Please get in touch for further information about our metabolic phenotyping service.