Hyperactivity and reduced energy cost of physical activity in serotonin 5-HT(2C) receptor mutant mice.
We have observed late-onset obesity in mutant mice lacking the serotonin 5-HT(2C) receptor. Despite chronically elevated food intake, young adult mutants exhibit neither elevated adiposity nor altered glucose or fat homeostasis. However, obesity subsequently develops after 6 months of age without increases in their level of hyperphagia. In this study, we investigated determinants of energy expenditure in 5-HT(2C) receptor mutant mice. Young adult mutants displayed patterns of elevated activity levels that were enhanced by fasting and tightly associated with repeated visits to a food source. Surprisingly, subsequent obesity development occurred despite persisting locomotor hyperactivity and without age-related declines in resting metabolic rate. Rather, substantial reductions in the energy cost of locomotor activity (LA) were observed in 5-HT(2C) receptor mutant mice. Moreover, both mutant and wild-type mice displayed age-related declines in the energy cost of LA, indicating that this process may be regulated by both aging and serotonergic signaling. These results indicate that a mutation of the 5-HT(2C) receptor gene (htr2c) increases LA, which contributes to the maintenance of normal body composition in young adult mutants despite their hyperphagia. Moreover, age-dependent reductions in the energy cost of physical activity could contribute to the subsequent development of late-onset obesity in 5-HT(2C) receptor mutant mice.
Nonogaki
Katsunori
K
Department of Psychiatry and Center for Neurobiology and Psychiatry, University of California, San Francisco, 94143, USA.
Abdallah
Luna
L
Goulding
Evan H
EH
Bonasera
Stephen J
SJ
Tecott
Laurence H
LH
D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D005215:Fasting; D005247:Feeding Behavior; D006948:Hyperkinesis / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology / Q000503:physiopathology; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014960:X Chromosome
D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin