Universität zu Köln

Rother, Eva, Belgardt, Bengt F., Tsaousidou, Eva ORCID: 0000-0003-2751-1911, Hampel, Brigitte, Waisman, Ari ORCID: 0000-0003-4304-8234, Myers, Martin G., Jr. and Bruening, Jens C. (2012). Acute selective ablation of rat insulin promoter-expressing (RIPHER) neurons defines their orexigenic nature. Proc. Natl. Acad. Sci. U. S. A., 109 (44). S. 18132 - 18138. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Rat insulin promoter (RIP)-expressing neurons in the hypothalamus control body weight and energy homeostasis. However, genetic approaches to study the role of these neurons have been limited by the fact that RIP expression is predominantly found in pancreatic beta-cells, which impedes selective targeting of neurons. To define the function of hypothalamic RIP-expressing neurons, we set out to acutely and selectively eliminate them via diphtheria toxin-mediated ablation. Therefore, the diphtheria toxin receptor transgene was specifically expressed upon RIP-specific Cre recombination using a RIP-Cre line first described by Herrera (RIPHER-Cre) [Herrera PL (2000) Development 127:2317-2322]. Using proopiomelanocortin-expressing cells located in the arcuate nucleus of the hypothalamus and in the pituitary gland as a model, we established a unique protocol of intracerebroventricular application of diphtheria toxin to efficiently ablate hypothalamic cells with no concomitant effect on pituitary proopiomelanocortin-expressing corticotrophs in the mouse. Using this approach to ablate RIPHER neurons in the brain, but not in the pancreas, resulted in decreased food intake and loss of body weight and fat mass. In addition, ablation of RIPHER neurons caused increased c-Fos immunoreactivity of neurons in the paraventricular nucleus (PVN) of the hypothalamus. Moreover, transsynaptic tracing of RIPHER neurons revealed labeling of neurons located in the PVN and dorsomedial hypothalamic nucleus. Thus, our experiments indicate that RIPHER neurons inhibit anorexigenic neurons in the PVN, revealing a basic orexigenic nature of these cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rother, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Belgardt, Bengt F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsaousidou, Eva UNSPECIFIED orcid.org/0000-0003-2751-1911 UNSPECIFIED Hampel, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Waisman, Ari UNSPECIFIED orcid.org/0000-0003-4304-8234 UNSPECIFIED Myers, Martin G., Jr. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-480830
DOI:	10.1073/pnas.1206147109
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	109
Number:	44
Page Range:	S. 18132 - 18138
Date:	2012
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL LINEAGE ABLATION; LEPTIN; CNS; PROOPIOMELANOCORTIN; MOUSE; HOMEOSTASIS; DEFICIENCY; RESISTANCE; HORMONE; WEIGHT Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48083