Serotonin 5-HT2C receptor-independent expression of hypothalamic NOR1, a novel modulator of food intake and energy balance, in mice.
NOR1, Nur77 and Nurr1 are orphan nuclear receptors and members of the NR4A subfamily. Here, we report that the expression of hypothalamic NOR1 was remarkably decreased in mildly obese beta-endorphin-deficient mice and obese db/db mice with the leptin receptor mutation, compared with age-matched wild-type mice, whereas there were no genotypic differences in the expression of hypothalamic Nur77 or Nurr1 in these animals. The injection of NOR1 siRNA oligonucleotide into the third cerebral ventricle significantly suppressed food intake and body weight in mice. On the other hand, the decreases in hypothalamic NOR1 expression were not found in non-obese 5-HT2C receptor-deficient mice. Moreover, systemic administration of m-chlorophenylpiperazine (mCPP), a 5-HT2C/1B receptor agonist, had no effect on hypothalamic NOR1 expression, while suppressing food intake in beta-endorphin-deficient mice. These findings suggest that 5-HT2C receptor-independent proopiomelanocortin-derived peptides regulate the expression of hypothalamic NOR1, which is a novel modulator of feeding behavior and energy balance.
Nonogaki
Katsunori
K
Center of Excellence, Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. knonogaki-tky@umin.ac.jp
Kaji
Takao
T
Ohba
Yukie
Y
Sumii
Makiko
M
Wakameda
Mamoru
M
Tamari
Tomohiro
T
D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004435:Eating; D004734:Energy Metabolism; D006963:Hyperphagia / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010879:Piperazines / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000096:biosynthesis* / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis* / Q000235:genetics; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis; D001615:beta-Endorphin / Q000172:deficiency / Q000235:genetics
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C539818:Nr4a1 protein, mouse; C539883:Nr4a2 protein, mouse; C490411:Nr4a3 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010879:Piperazines; D034741:RNA, Small Interfering; D044405:Receptor, Serotonin, 5-HT2C; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D014157:Transcription Factors; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; C015068:1-(3-chlorophenyl)piperazine