Abstract
Serotonin (5-HT) is a central inhibitor of food intake in mammals. Thus far, the intracellular mechanisms for the effect of serotonin on appetite regulation remain unclear. It has been recently demonstrated that reactive oxygen species (ROS) in the hypothalamus are a crucial integrative target for the regulation of food intake. To investigate the role of ROS in the serotonin-induced anorexigenic effects, conscious mice were treated with 5-HT alone or combination with Trolox (a ROS scavenger) or Apocynin (an NADPH oxidase inhibitor) by acute intracerebroventricular injection. Both Trolox and Apocynin reversed the anorexigenic action of 5-HT and the 5-HT-induced hypothalamic ROS elevation. The mRNA and protein expression levels of pro-opiomelanocortin (POMC) were dramatically increased after ICV injection with 5-HT. The anorexigenic action of 5-HT was accompanied by markedly elevated hypothalamic MDA levels and GSH-Px activity, while the SOD activity was decreased. Moreover, 5-HT significantly increased the mRNA expression of UCP-2 but reduced the levels of UCP-3. Both Trolox and Apocynin could block the 5-HT-induced changes in UCP-2 and UCP-3 gene expression. Our study demonstrates for the first time that the anorexigenic effect of 5-HT is mediated by the generation of ROS in the hypothalamus through an NADPH oxidase-dependent pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetophenones / pharmacology
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Animals
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Antioxidants / pharmacology
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Blotting, Western
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Chromans / pharmacology
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Eating / drug effects*
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Gene Expression / drug effects
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Glutathione Peroxidase / metabolism
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Hypothalamus / drug effects
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Hypothalamus / metabolism
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Injections, Intraventricular
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Ion Channels / genetics
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Ion Channels / metabolism
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Male
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Malondialdehyde / metabolism
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Mice
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism
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NADPH Oxidases / metabolism*
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Pro-Opiomelanocortin / genetics
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Pro-Opiomelanocortin / metabolism
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Reactive Oxygen Species / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Serotonin / administration & dosage
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Serotonin / pharmacology*
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Serotonin Receptor Agonists / administration & dosage
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Serotonin Receptor Agonists / pharmacology
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Superoxide Dismutase / metabolism
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Uncoupling Protein 2
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Uncoupling Protein 3
Substances
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Acetophenones
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Antioxidants
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Chromans
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Ion Channels
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Mitochondrial Proteins
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Reactive Oxygen Species
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Serotonin Receptor Agonists
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Ucp2 protein, mouse
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Ucp3 protein, mouse
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Uncoupling Protein 2
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Uncoupling Protein 3
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Serotonin
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Malondialdehyde
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Pro-Opiomelanocortin
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acetovanillone
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Glutathione Peroxidase
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Superoxide Dismutase
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NADPH Oxidases
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6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
Grants and funding
This work was supported by grants from the National Basic Research Program of China- the 973 Program (2012CB124701; 2009CB941601) and the National Natural Science Foundation of China (30871845). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript