At the same time, he says, the energy-expenditure mechanism could prove a target for therapy, offering the recipient more "bang for the buck of exercise." A possible candidate for such a target, he says, is the serotonin 5-HT(2c) receptor.
Mice genetically engineered to lack the 5-HT(2c) serotonin receptor demonstrated the most dramatic results in the study. Young adult mutants spent their days scurrying back and forth to the feeder with a peripatetic urgency, yet despite their perpetual consumption they maintained normal body weight. It was only upon reaching middle age that they became obese. At nine to 10 months of age, they used significantly less energy during activity than either the younger mutant mice or the normal middle-aged mice.
Middle-aged normal mice, which gradually gain weight as they age, also burned less energy during activity than younger normal mice, despite eating the same moderate amount of food and maintaining the same resting metabolic rate.
The pronounced results in the mature mutant mice the onset of obesity associated with the dramatic decrease in energy expenditure during exercise -- suggest, says Tecott, that energy cost may be regulated both by aging and serotonergic signaling. This wouldn't necessarily suggest that mutations in the 5-HT(2c) serotonin receptor cause middle-age obesity in humans, but rather that the receptor might influence factors involved in energy expenditure and therefore could prove a target for therapy.
The amount of energy expended during physical activity is measured by the amount of oxygen that is used by the body during a specified period, in relation to weight and distant traveled. The measurement reflects the central nervous system's response to a complex set of variables related to body composition & energy metabolism, or the buildup and breakdown of energy.
There are several mechanis
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Contact: Jennifer OBrien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
6-Feb-2003