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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Rathjen Thomas, Yan Xin, Kononenko Natalia L, Ku Min-Chi, Song Kun, Ferrarese Leiron, Tarallo Valentina, Puchkov Dmytro, Kochlamazashvili Gaga, Brachs Sebastian, Varela Luis, Szigeti-Buck Klara, Yi Chun-Xia, Schriever Sonja C, Tattikota Sudhir Gopal, Carlo Anne Sophie, Moroni Mirko, Siemens Jan, Heuser Arnd, van der Weyden Louise, Birkenfeld Andreas L, Niendorf Thoralf, Poulet James F A, Horvath Tamas L, Trajkovski Mirko, HauckeV, PoyMN,
Project Metabolic homeostasis through physiological stimulation of beige fat development
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Original article (peer-reviewed)

Journal Nature Neuroscience
Volume (Issue) 20(8)
Page(s) 1096 - 1103
Title of proceedings Nature Neuroscience
DOI 10.1038/nn.4590

Open Access

Type of Open Access Website


usceptibility 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.