Universität zu Köln

Loehr, Heiko, Hess, Simon, Pereira, Mafalda M. A., Reinoss, Philip, Leibold, Sandra, Schenkel, Christel, Wunderlich, Claudia M., Kloppenburg, Peter, Bruening, Jens C. and Hammerschmidt, Matthias (2018). Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit. Cell Reports, 23 (6). S. 1728 - 1742. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Anorexigenic pro-opiomelanocortin (Pomc)/alpha-melanocyte stimulating hormone (alpha MSH) neurons of the hypothalamic melanocortin system function as key regulators of energy homeostasis, also controlling somatic growth across different species. However, the mechanisms of melanocortin-dependent growth control still remain ill-defined. Here, we reveal a thus-far-unrecognized structural and functional connection between Pomc neurons and the somatotropic hypothalamo-pituitary axis. Excessive feeding of larval zebrafish causes leptin resistance and reduced levels of the hypothalamic satiety mediator pomca. In turn, this leads to reduced activation of hypophysiotropic somatostatin (Sst)-neurons that express the melanocortin receptor Mc4r, elevated growth hormone (GH) expression in the pituitary, and enhanced somatic growth. Mc4r expression and alpha MSH responsiveness are conserved in Sst-expressing hypothalamic neurons of mice. Thus, acquired leptin resistance and attenuation of pomca transcription in response to excessive caloric intake may represent an ancient mechanism to promote somatic growth when food resources are plentiful.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Loehr, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Hess, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Pereira, Mafalda M. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinoss, Philip UNSPECIFIED UNSPECIFIED UNSPECIFIED Leibold, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Schenkel, Christel UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, Claudia M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloppenburg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammerschmidt, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-186569
DOI:	10.1016/j.celrep.2018.04.018
Journal or Publication Title:	Cell Reports
Volume:	23
Number:	6
Page Range:	S. 1728 - 1742
Date:	2018
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENERGY HOMEOSTASIS; SOMATOTROPIC AXIS; PROOPIOMELANOCORTIN DEFICIENCY; AGRP NEURONS; FINAL HEIGHT; OBESITY; ZEBRAFISH; MELANOCORTIN; RECEPTOR; MOUSE Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18656