Universität zu Köln

Shainer, Inbal ORCID: 0000-0001-5487-8925, Michel, Maximilian ORCID: 0000-0002-5910-5363, Marquart, Gregory D., Bhandiwad, Ashwin A., Zmora, Nilli, Livne, Zohar Ben-Moshe, Zohar, Yonathan, Hazak, Adi, Mazon, Yael, Foerster, Dominique, Hollander-Cohen, Lian, Cone, Roger D., Burgess, Harold A. and Gothilf, Yoav ORCID: 0000-0002-6054-4128 (2019). Agouti-Related Protein 2 Is a New Player in the Teleost Stress Response System. Curr. Biol., 29 (12). S. 2009 - 2027. CAMBRIDGE: CELL PRESS. ISSN 1879-0445

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Shainer, Inbal UNSPECIFIED orcid.org/0000-0001-5487-8925 UNSPECIFIED Michel, Maximilian UNSPECIFIED orcid.org/0000-0002-5910-5363 UNSPECIFIED Marquart, Gregory D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bhandiwad, Ashwin A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zmora, Nilli UNSPECIFIED UNSPECIFIED UNSPECIFIED Livne, Zohar Ben-Moshe UNSPECIFIED UNSPECIFIED UNSPECIFIED Zohar, Yonathan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hazak, Adi UNSPECIFIED UNSPECIFIED UNSPECIFIED Mazon, Yael UNSPECIFIED UNSPECIFIED UNSPECIFIED Foerster, Dominique UNSPECIFIED UNSPECIFIED UNSPECIFIED Hollander-Cohen, Lian UNSPECIFIED UNSPECIFIED UNSPECIFIED Cone, Roger D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Burgess, Harold A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gothilf, Yoav UNSPECIFIED orcid.org/0000-0002-6054-4128 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-137691
DOI:	10.1016/j.cub.2019.05.021
Journal or Publication Title:	Curr. Biol.
Volume:	29
Number:	12
Page Range:	S. 2009 - 2027
Date:	2019
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1879-0445
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IN-VIVO; ZEBRAFISH; NEURONS; AGRP; IDENTIFICATION; EXPRESSION; MELATONIN; RECEPTOR; ABLATION; CELLS Multiple languages Biochemistry & Molecular Biology; Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13769