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UCSF study suggests novel factor could contribute to adult obesity

ms through which mutations in the 5-HT(2c) receptor could alter the input into this highly orchestrated system, says Tecott. The receptor may modulate neuro-endocrine function and/or sympathetic nervous system activity, thereby regulating such factors as glucose, fat metabolism, skeletal muscle oxygenation and leptin signaling.

If this proved the case, a drug that stimulated the serotonin 5-HT(2c) receptor might decrease the energy efficiency of physical activity, says Tecott. He and his colleagues now are testing this possibility in normal mice.

Notably, serotonin receptors are already the target of numerous drugs that enhance serotonergic transmission, including the appetite suppressant fenfluramine and the depression-treating serotonin reuptake inhibitors. In prior work, Tecott's team found that the appetite-suppressant effects of fenfluramine were reduced in the 5-HT(2c) receptor mutant mice, implicating the receptor as a target for appetite suppression.

It may be, says Tecott, that in addition to being an appetite suppressor fenfluramine affects energy expenditure. In any case, he says, further studies on the novel physiological process could help explain why some mammals, including mice and humans, tend to get heavier as they get older.

Co-authors of the study were Katsunori Nonogaki PhD, Luna Abdallah, PhD, postdoctoral fellow, Evan H. Goulding, MD, PhD, postdoctoral fellow, and Stephen J. Bonasera, MD, PhD, postdoctoral fellow, all members of the Tecott lab at the time of the studies.


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Contact: Jennifer OBrien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
6-Feb-2003


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