Maintenance of body weight relies on the fine control of the balance between energy intake and energy expenditure. Obesity or leanness results when food intake exceeds or is lower than energy expenditure. Energy can be expended by performing work (e.g. locomotor respiratory and cardiac activities) or producing heat (thermogenesis).
The body has the ability to utilize and transition between various fuels (such as carbohydrate, lipid and proteins), and to transition between these in response to hormonal, chiefly insulin, and substrate signals, as during the fasting to feeding transition. This plasticity can be altered in transgenic mice models, or lost due to obesity and type 2 DM.
The Comprehensive Lab Animal Monitoring System (CLAMS) (Columbus Instruments, Columbus, OH) consists of 12 individual live-in cages for mice that allow automated, non-invasive evaluation of energy intake and energy expenditure, as well as metabolic substrate selection. Each cage is an indirect open circuit calorimeter (Oxymax) that provides measures of oxygen consumption (VO2) and carbon dioxide production (VCO2). The Respiratory Exchange Ratio no-protein (no-protein RER, or respiratory quotient VCO2/VO2), is used to estimate substrate disappearance rates. Heat production is estimated from oxygen consumption and from the RER. The system also concurrently measures food and water consumption, and locomotor activity.
Mice are acclimated to the metabolic cages for 48 hours prior to the experiment. Data are collected for 1 to 3 consecutive 24-hour periods with a 12:12 light:dark cycle. Access to food can be controlled online for measurements of the metabolic response to fasting/refeeding patterns.
A minimum of 8 mice per group should be sent to our facility, one week prior to the experiment.
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Becattini B, Marone R, Zani F, Arsenijevic D, Seydoux J, Montani JP, Dulloo AG, Thorens B, Preitner B, Wymann MP, Solinas G. PI3Kγ within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance. Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):E854-63.