title: Feeding and stress interact through the serotonin 2C receptor in developing mice.
abstract: Feeding and stress neurocircuits are intertwined. Among the neurotransmitters and receptors common to both circuits, the serotonin 2C receptor is particularly intriguing because its distribution is limited to the central nervous system. Hence, deficits in energy balance and stress responses in mice lacking this gene are likely due to defects in central regulation. The phenotype of the serotonin 2C receptor null (KO) mouse is adult-onset hyperphagia, depressed metabolic rate, and disruption in satiety, with a progression to midlife obesity. A provocative feature of this obese model is our recent finding of a childhood component where the KO mouse is heavier at weaning, a distinction that only returns in adulthood. To determine when the KO mouse becomes heavier, longitudinal and cross-sectional timecourse studies followed weight gain and found significantly heavier body weight, higher plasma leptin, and rectal temperature, only in unhandled KO compared to sibling wildtype controls. To map what metabolic compensations cause the KO weight increase, we launched thermal and behavioral studies in 10 day old mice before there was any genotype difference in body weight, corticosterone levels, or the levels leptin during the developmental leptin peak. The heavier KO weanling is, in part, explained by hyperphagia, lower metabolic rate and activity, and behavioral thermogenesis measured at 10 days of age. However, the infant KO mouse is stress-sensitive and growth is impaired with handling. The serotonin 2C receptor has a role in fine-tuning energetic and stress demands even as neurocircuits are developing, and unbalanced compensations in infancy may program responses in adulthood that are "off target" from optimal function.
authors.affiliation: Department of Physiology, Box 0444, University of California San Francisco, San Francisco, CA 94132-0444, United States. Susan.Akana@ucsf.edu
authors.forename: Susan F
authors.initials: SF
authors.lastname: Akana
mesh_terms: D052242:Adiponectin / Q000097:blood; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001069:Appetite Regulation / Q000502:physiology*; D001833:Body Temperature Regulation / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003430:Cross-Sectional Studies; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D006963:Hyperphagia / Q000150:complications / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000097:blood; D010641:Phenotype; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism*; D014886:Weaning; D015430:Weight Gain / Q000502:physiology
chemical_list: D052242:Adiponectin; D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y; D044405:Receptor, Serotonin, 5-HT2C; D003345:Corticosterone