Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1
Autor: | Tamas L. Horvath, Louise van der Weyden, Chun-Xia Yi, Xin Yan, Valentina Tarallo, Andreas L. Birkenfeld, Dmytro Puchkov, Min Chi Ku, Anne Sophie Carlo, Sonja C. Schriever, Jan Siemens, Volker Haucke, Kun Song, Arnd Heuser, Luis Varela, Sudhir Gopal Tattikota, James F.A. Poulet, Mirko Moroni, Matthew N. Poy, Mirko Trajkovski, Matthias H. Tschöp, Natalia L. Kononenko, Thoralf Niendorf, Leiron Ferrarese, Gaga Kochlamazashvili, Matthias Heinig, Thomas Rathjen, Klara Szigeti-Buck, Sebastian Brachs |
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Přispěvatelé: | AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Aging & Later Life, ANS - Cellular & Molecular Mechanisms, Endocrinology Laboratory, Endocrinology, ACS - Diabetes & metabolism |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Pro-Opiomelanocortin Neurons/metabolism Obesity/genetics Energy homeostasis Cell Adhesion Molecules Neuronal/genetics 0302 clinical medicine Homeostasis 2. Zero hunger Neurons Pro-Opiomelanocortin/metabolism Cell adhesion molecule General Neuroscience Hypothalamus Arcuate Nucleus of Hypothalamus/metabolism Cell Adhesion Molecules/genetics medicine.medical_specialty Transgene Cell Adhesion Molecules Neuronal Immunoglobulins Mice Transgenic Neurotransmission Biology Energy Metabolism/physiology Article 03 medical and health sciences Arcuate nucleus Internal medicine medicine Animals Obesity ddc:612 Body Weight Arcuate Nucleus of Hypothalamus Cell Adhesion Molecule-1 Membrane Proteins Homeostasis/genetics Immunoglobulins/genetics 030104 developmental biology Endocrinology Membrane protein Body Weight/physiology Membrane Proteins/metabolism Energy Metabolism Neuronal Cell Adhesion Molecule Neuroscience Cell Adhesion Molecules 030217 neurology & neurosurgery Genome-Wide Association Study |
Zdroj: | Nature neuroscience Nature Neuroscience Nat. Neurosci. 20, 1096-1103 (2017) Nature neuroscience, 20(8), 1096-1103. Nature Publishing Group Nature neuroscience, Vol. 20, No 8 (2017) pp. 1096-1103 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 2017, ' Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1 ', Nature Neuroscience, vol. 20, no. 8, pp. 1096-1103 . https://doi.org/10.1038/nn.4590 |
ISSN: | 1546-1726 1097-6256 |
Popis: | 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. |
Databáze: | OpenAIRE |
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