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A negative feedback system between brain serotonin systems and plasma active ghrelin levels in mice
Katsunori Nonogaki1, Kana Ohashi-Nozue, Yoshitomo Oka
1Center of Excellence, Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan. knonogaki-tky@umin.ac.jp
Biochemical and Biophysical Research Communications
|January 25, 2006
Summary
Fasting increases brain serotonin receptor gene expression and plasma ghrelin. Serotonin drugs reduce ghrelin and impact appetite-regulating genes, suggesting a brain serotonin-ghrelin feedback loop for energy balance.
Area of Science:
- Neuroscience
- Endocrinology
- Molecular Biology
Background:
- Brain serotonin (5-hydroxytryptamine; 5-HT) systems regulate eating behavior and energy homeostasis.
- Specific serotonin receptors (5-HT2C and 5-HT1B) mediate anorexic effects of certain drugs.
- Ghrelin is a key hormone involved in appetite regulation and energy balance.
Purpose of the Study:
- To investigate the relationship between brain serotonin systems and plasma active ghrelin levels during fasting in mice.
- To examine the effects of serotonin-releasing and reuptake-inhibiting drugs on gene expression related to appetite regulation.
Main Methods:
- Mice were subjected to a 24-hour fasting or fed state.
- Expression of hypothalamic 5-HT2C and 5-HT1B receptor genes was measured.
- Plasma active ghrelin levels were quantified.
- Mice were treated with m-chlorophenylpiperazine (mCPP) or fenfluramine, and the expression of appetite-regulating genes (POMC, CART, NPY, AgRP, ghrelin) was analyzed.
Main Results:
- Fasting increased hypothalamic 5-HT2C and 5-HT1B receptor gene expression and plasma active ghrelin levels.
- Treatment with mCPP or fenfluramine inhibited fasting-induced increases in plasma active ghrelin.
- mCPP or fenfluramine increased hypothalamic pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) gene expression.
- These drugs did not significantly affect hypothalamic neuropeptide Y (NPY), agouti-related protein (AgRP), or ghrelin gene expression.
Conclusions:
- A negative feedback system exists between brain serotonin systems and plasma active ghrelin levels in regulating energy homeostasis in mice.
- Serotonin pathways may influence appetite through modulation of ghrelin and key anorexigenic gene expression.
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