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Published on: November 15, 2013
Altered gene expressions involved in energy expenditure in 5-HT(2C) receptor mutant mice
Katsunori Nonogaki1, Riaz A Memon, Carl Grunfeld
1Department of Psychiatry and Center for Neurobiology and Psychiatry, University of California, San Francisco, CA 94143, USA. nonogaki@med.nagoya-u.ac.jp
Abstract:
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.
Insights
Mice lacking the serotonin 5-HT(2C) receptor develop obesity due to increased appetite. This study reveals reduced oxygen consumption and altered gene expression, including beta 3-adrenergic receptor, in these obese mice.
Area of Science:
- Neuroscience
- Metabolic Research
- Genetics
Background:
- Serotonin 5-HT(2C) receptors play a role in regulating appetite and energy balance.
- Mutations in this receptor can lead to hyperphagia and obesity.
Purpose of the Study:
- To investigate the metabolic consequences of a null mutation in the serotonin 5-HT(2C) receptor gene.
- To explore the impact on energy expenditure and gene expression related to adiposity.
Main Methods:
- Utilized genetically modified mice with a targeted null mutation of the serotonin 5-HT(2C) receptor gene.
- Measured oxygen consumption in fed and fasted states.
- Analyzed mRNA levels of uncoupling proteins (UCP-1, UCP-2, UCP-3) and beta 3-adrenergic receptors (beta 3-AR) in various tissues.
Main Results:
- Obese mutant mice exhibited decreased oxygen consumption.
- UCP-2 mRNA levels were significantly increased in white adipose tissue and skeletal muscle, and in the liver of both young and old mutants.
- Age-dependent decreases in beta 3-AR mRNA were observed in white adipose tissue of mutants, correlating with enhanced adiposity.
Conclusions:
- A mutation in the serotonin 5-HT(2C) receptor gene leads to hyperphagia and obesity.
- The observed metabolic changes include reduced oxygen consumption and altered expression of genes involved in energy metabolism.
- The study suggests a secondary decrease in beta 3-AR gene expression is linked to the enhanced adiposity in these mutants.
