title: Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons.
abstract: Adiponectin secreted from adipose tissues plays a role in the regulation of energy homeostasis, food intake, and reproduction in the hypothalamus. We have previously demonstrated that adiponectin significantly inhibited GNRH secretion from GT1-7 hypothalamic GNRH neuron cells. In this study, we further investigated the effect of adiponectin on hypothalamic KISS1 gene transcription, which is the upstream signal of GNRH. We found that globular adiponectin (gAd) or AICAR, an artificial AMPK activator, decreased KISS1 mRNA transcription and promoter activity. Conversely, inhibition of AMPK by Compound C or AMPKα1-SiRNA augmented KISS1 mRNA transcription and promoter activity. Additionally, gAd and AICAR decreased the translocation of specificity protein-1 (SP1) from cytoplasm to nucleus; however, Compound C and AMPKα1-siRNA played an inverse role. Our experiments in vivo demonstrated that the expression of Kiss1 mRNA was stimulated twofold in the Compound C-treated rats and decreased about 60-70% in gAd- or AICAR-treated rats compared with control group. The numbers of kisspeptin immunopositive neurons in the arcuate nucleus region of Sprague Dawley rats mimicked the same trend seen in Kiss1 mRNA levels in animal groups with different treatments. In conclusion, our results provide the first evidence that adiponectin reduces Kiss1 gene transcription in GT1-7 cells through activation of AMPK and subsequently decreased translocation of SP1.
authors.affiliation: Department of Endocrinology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, China. wenjunping@medmail.com.cn
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Wen
authors.forename: Chune
authors.initials: C
authors.lastname: Liu
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Bi
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Hu
authors.forename: Qingshi
authors.initials: Q
authors.lastname: Chen
authors.forename: Huibing
authors.initials: H
authors.lastname: Huang
authors.forename: Ji-Xing
authors.initials: JX
authors.lastname: Liang
authors.forename: Lian-Tao
authors.initials: LT
authors.lastname: Li
authors.forename: Li-Xiang
authors.initials: LX
authors.lastname: Lin
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism / Q000502:physiology*; D052242:Adiponectin / Q000494:pharmacology* / Q000502:physiology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology; D016329:Sp1 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D052242:Adiponectin; C491406:Kiss1 protein, rat; D059648:Kisspeptins; D012265:Ribonucleotides; D016329:Sp1 Transcription Factor; D000620:Aminoimidazole Carboxamide; D000263:Adenylate Kinase; C031143:AICA ribonucleotide