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Rathjen, T.* ; Yan, X.* ; Kononenko, N.L.* ; Ku, M.C.* ; Song, K.* ; Ferrarese, L.* ; Tarallo, V.* ; Puchkov, D.* ; Kochlamazashvili, G.* ; Brachs, S.* ; Varela, L.* ; Szigeti-Buck, K.* ; Yi, C.-X. ; Schriever, S.C. ; Tattikota, S.G.* ; Carlo, A.S.* ; Moroni, M.* ; Siemens, J.* ; Heuser, A.* ; van der Weyden, L.* ; Birkenfeld, A.L. ; Niendorf, T.* ; Poulet, J.F.A.* ; Horvath, T.L.* ; Tschöp, M.H. ; Heinig, M. ; Trajkovski, M.* ; Haucke, V.* ; Poy, M.N.*

Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1.

Nat. Neurosci. 20, 1096-1103 (2017)
Postprint DOI PMC
Open Access Green
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Genome-wide Association; Pomc Neurons; Synaptic Adhesion; Arcuate Nucleus; Leptin Action; Mass Index; Syncam 1; Insulin; Obesity; Brain
ISSN (print) / ISBN 1097-6256
e-ISSN 1546-1726
Zeitschrift Nature Neuroscience
Quellenangaben Band: 20, Heft: 8, Seiten: 1096-1103 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Computational Biology (ICB)
Institute for Pancreatic Beta Cell Research (IPI)