title: Agouti-related protein (AGRP) is conserved and regulated by metabolic state in the zebrafish, Danio rerio.
abstract: Agouti-related protein (AGRP) and proopiomelanocortin (POMC) genes encode secreted hypothalamic factors regulated by metabolic state in mammals and are involved in energy homeostasis. The zebrafish, Danio rerio, is a model system for forward genetics in vertebrates: POMC and AGRP in this organism have not been well characterized. Toward this end, AGRP and POMC were cloned from zebrafish. Zebrafish AGRP cDNA encodes a 127-amino-acid protein 36% and 40% identical to human and mouse AGRP, respectively. Zebrafish POMC cDNA encodes a 222-amino-acid preprohormone. Sequence identity to the mammalian ortholog is about 50%. Zebrafish AGRP and POMC transcripts were detected at 24 h post-fertilization (hpf) by RTPCR, and in situ hybridization demonstrated zebrafish AGRP mRNA exclusively in hypothalamus and POMC mRNA in hypothalamus and pituitary. Fasting did not alter POMC transcript levels, while AGRP transcripts were significantly upregulated. The ratio of AGRP/POMC transcripts in adult brain was increased up to threefold by fasting. These results demonstrate that the melanocortin system is regulated by metabolic state in zebrafish, and this finding thus provides a vertebrate system for the genetic analysis of the role of the melanocortin system in energy homeostasis.
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, OR 97239-3098, USA.
authors.forename: Youngsup
authors.initials: Y
authors.lastname: Song
authors.forename: Gregory
authors.initials: G
authors.lastname: Golling
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Thacker
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cone
mesh_terms: D054369:Agouti-Related Protein; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D005508:Food Deprivation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012313:RNA; D011333:Pro-Opiomelanocortin