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
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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