Rathjen, Thomas, Yan, Xin ORCID: 0000-0002-9135-7915, Kononenko, Natalia L., Ku, Min-Chi ORCID: 0000-0003-0963-2461, Song, Kun ORCID: 0000-0001-6216-8157, Ferrarese, Leiron, Tarallo, Valentina, Puchkov, Dmytro ORCID: 0000-0001-8341-4847, Kochlamazashvili, Gaga, Brachs, Sebastian ORCID: 0000-0002-6336-3939, Varela, Luis, Szigeti-Buck, Klara, Yi, Chun-Xia ORCID: 0000-0003-1184-4615, Schriever, Sonja C., Tattikota, Sudhir Gopal ORCID: 0000-0003-0318-5533, Carlo, Anne Sophie, Moroni, Mirko, Siemens, Jan, Heuser, Arnd, van der Weyden, Louise, Birkenfeld, Andreas L. ORCID: 0000-0003-1407-9023, Niendorf, Thoralf, Poulet, James F. A., Horvath, Tamas L., Tschop, Matthias H., Heinig, Matthias ORCID: 0000-0002-5612-1720, Trajkovski, Mirko ORCID: 0000-0002-3152-9551, Haucke, Volker and Poy, Matthew N. (2017). Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1. Nat. Neurosci., 20 (8). S. 1096 - 1107. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1726

Full text not available from this repository.

Abstract

Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure. Loss of Cadm1 protected mice from obesity, and tract-tracing analysis revealed Cadm1-positive innervation of POMC neurons via afferent projections originating from beyond the arcuate nucleus. Reducing Cadm1 expression in the hypothalamus and hippocampus promoted a negative energy balance and weight loss. These data identify essential roles for Cadm1-mediated neuronal input in weight regulation and provide insight into the central pathways contributing to human obesity.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rathjen, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yan, XinUNSPECIFIEDorcid.org/0000-0002-9135-7915UNSPECIFIED
Kononenko, Natalia L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ku, Min-ChiUNSPECIFIEDorcid.org/0000-0003-0963-2461UNSPECIFIED
Song, KunUNSPECIFIEDorcid.org/0000-0001-6216-8157UNSPECIFIED
Ferrarese, LeironUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tarallo, ValentinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puchkov, DmytroUNSPECIFIEDorcid.org/0000-0001-8341-4847UNSPECIFIED
Kochlamazashvili, GagaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brachs, SebastianUNSPECIFIEDorcid.org/0000-0002-6336-3939UNSPECIFIED
Varela, LuisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szigeti-Buck, KlaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yi, Chun-XiaUNSPECIFIEDorcid.org/0000-0003-1184-4615UNSPECIFIED
Schriever, Sonja C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tattikota, Sudhir GopalUNSPECIFIEDorcid.org/0000-0003-0318-5533UNSPECIFIED
Carlo, Anne SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moroni, MirkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siemens, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heuser, ArndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Weyden, LouiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Birkenfeld, Andreas L.UNSPECIFIEDorcid.org/0000-0003-1407-9023UNSPECIFIED
Niendorf, ThoralfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poulet, James F. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horvath, Tamas L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tschop, Matthias H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinig, MatthiasUNSPECIFIEDorcid.org/0000-0002-5612-1720UNSPECIFIED
Trajkovski, MirkoUNSPECIFIEDorcid.org/0000-0002-3152-9551UNSPECIFIED
Haucke, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poy, Matthew N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-224255
DOI: 10.1038/nn.4590
Journal or Publication Title: Nat. Neurosci.
Volume: 20
Number: 8
Page Range: S. 1096 - 1107
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1546-1726
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; POMC NEURONS; SYNAPTIC ADHESION; ARCUATE NUCLEUS; LEPTIN ACTION; MASS INDEX; SYNCAM 1; INSULIN; OBESITY; BRAINMultiple languages
NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22425

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item