A negative feedback system between brain serotonin systems and plasma active ghrelin levels in mice.
Brain serotonin (5-hydroxytryptamine; 5-HT) systems contribute to regulate eating behavior and energy homeostasis. 5-HT2C receptors and 5-HT1B receptors have been shown to mediate anorexic effects of 5-HT drugs such as d-fenfluramine, which stimulates 5-HT release and inhibits 5-HT reuptake, and m-chlorophenylpiperazine (mCPP), a 5-HT2C receptor agonist. Here, we report that 24-h fasting increased the expression of hypothalamic 5-HT2C receptor and 5-HT1B receptor genes in association with increases in plasma active ghrelin levels compared with fed state in mice. Treatment with mCPP or fenfluramine significantly inhibited the increases in plasma active ghrelin levels. mCPP or fenfluramine significantly increased the expression of hypothalamic pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript genes while having no significant effects on the expression of hypothalamic neuropeptide Y, agouti- related protein, and ghrelin genes. These results suggest that there is a negative feedback system between brain 5-HT systems and plasma active ghrelin levels in energy homeostasis in mice.
Nonogaki
Katsunori
K
Center of Excellence, Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan. knonogaki-tky@umin.ac.jp
Ohashi-Nozue
Kana
K
Oka
Yoshitomo
Y
D000821:Animal Feed; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005215:Fasting; D025461:Feedback, Physiological; D005277:Fenfluramine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D054439:Ghrelin; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036361:Peptide Hormones / Q000097:blood*; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D012701:Serotonin / Q000378:metabolism*
D054439:Ghrelin; D036361:Peptide Hormones; D010879:Piperazines; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D005277:Fenfluramine; D012701:Serotonin; C015068:1-(3-chlorophenyl)piperazine