Altered gene expressions involved in energy expenditure in 5-HT(2C) receptor mutant mice.
Mice with a targeted null mutation of the serotonin 5-HT(2C) receptor gene exhibit hyperphagia that leads to a late-onset obesity. Here we show that oxygen consumption was decreased in fed and fasted obese mutants. No phenotypic differences were observed in uncoupling protein-1 (UCP-1) mRNA levels in brown adipose tissues and UCP-3 mRNA in skeletal muscle. UCP-2 mRNA levels were significantly increased in white adipose tissue (4-fold) and skeletal muscle (47%) in older obese mutant mice, whereas UCP-2 mRNA in liver are significantly increased in both young lean (54% increase) and older obese (52% increase) mutant mice. In contrast, 5-HT(2C) receptor mutants displayed age-dependent decreases in beta 3-adrenergic receptor (beta 3-AR) mRNA levels in white adipose tissue, however, no such changes were observed in brown adipose tissue. These results indicate that a mutation of 5-HT(2C) receptor gene leads to a secondary decrease in beta 3-AR gene expression that is related to enhanced adiposity.
Nonogaki
Katsunori
K
Department of Psychiatry and Center for Neurobiology and Psychiatry, University of California, San Francisco, CA 94143, USA. nonogaki@med.nagoya-u.ac.jp
Memon
Riaz A
RA
Grunfeld
Carl
C
Feingold
Kenneth R
KR
Tecott
Laurence H
LH
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D017931:DNA Primers; D004734:Energy Metabolism; D015870:Gene Expression / Q000502:physiology*; D006963:Hyperphagia / Q000235:genetics; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins; D009765:Obesity / Q000235:genetics; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D017931:DNA Primers; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D022702:Receptors, Adrenergic, beta-3; D011985:Receptors, Serotonin; C000604372:Ucp1 protein, mouse; C000604393:Ucp3 protein, mouse; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3