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

Tools

Item Type:	Article
Title:	Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1
Creators Name:	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. and Poy, M.N.
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.
Keywords:	Arcuate Nucleus of Hypothalamus, Body Weight, Cell Adhesion Molecules, Energy Metabolism, Genome-Wide Association Study, Homeostasis, Immunoglobulins, Membrane Proteins, Neuronal Cell Adhesion Molecules, Neurons, Obesity, Pro-Opiomelanocortin, Transgenic Mice, Animals, Mice
Source:	Nature Neuroscience
ISSN:	1097-6256
Publisher:	Nature Publishing Group
Volume:	20
Number:	8
Page Range:	1096-1103
Date:	August 2017
Official Publication:	https://doi.org/10.1038/nn.4590
External Fulltext:	View full text on PubMed Central Europe
PubMed:	View item in PubMed

Repository Staff Only: item control page