RRC ID 60012
Author Shainer I, Michel M, Marquart GD, Bhandiwad AA, Zmora N, Ben-Moshe Livne Z, Zohar Y, Hazak A, Mazon Y, Förster D, Hollander-Cohen L, Cone RD, Burgess HA, Gothilf Y.
Title Agouti-Related Protein 2 Is a New Player in the Teleost Stress Response System.
Journal Curr Biol
Abstract Agouti-related protein (AgRP) is a hypothalamic regulator of food consumption in mammals. However, AgRP has also been detected in circulation, but a possible endocrine role has not been examined. Zebrafish possess two agrp genes: hypothalamically expressed agrp1, considered functionally equivalent to the single mammalian agrp, and agrp2, which is expressed in pre-optic neurons and uncharacterized pineal gland cells and whose function is not well understood. By ablation of AgRP1-expressing neurons and knockout of the agrp1 gene, we show that AgRP1 stimulates food consumption in the zebrafish larvae. Single-cell sequencing of pineal agrp2-expressing cells revealed molecular resemblance to retinal-pigment epithelium cells, and anatomic analysis shows that these cells secrete peptides, possibly into the cerebrospinal fluid. Additionally, based on AgRP2 peptide localization and gene knockout analysis, we demonstrate that pre-optic AgRP2 is a neuroendocrine regulator of the stress axis that reduces cortisol secretion. We therefore suggest that the ancestral role of AgRP was functionally partitioned in zebrafish by the two AgRPs, with AgRP1 centrally regulating food consumption and AgRP2 acting as a neuroendocrine factor regulating the stress axis.
Volume 29(12)
Pages 2009-2019.e7
Published 2019-6-17
DOI 10.1016/j.cub.2019.05.021
PII S0960-9822(19)30556-1
PMID 31178320
MeSH Animals Gene Knockout Techniques Hypothalamus / metabolism Intracellular Signaling Peptides and Proteins / genetics* Intracellular Signaling Peptides and Proteins / metabolism Pineal Gland / metabolism Stress, Physiological / genetics* Zebrafish / genetics Zebrafish / physiology* Zebrafish Proteins / genetics* Zebrafish Proteins / metabolism
IF 9.193
Times Cited 3
Zebrafish Tg(gad1b:GFP)