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

Thomas Rathjen; Xin Yan; Natalia L. Kononenko; Min Chi Ku; Kun Song; Leiron Ferrarese; Valentina Tarallo; Dmytro Puchkov; Gaga Kochlamazashvili; Sebastian Brachs; Luis Varela; Klara Szigeti-Buck; Chun Xia Yi; Sonja C. Schriever; Sudhir Gopal Tattikota; Anne Sophie Carlo; Mirko Moroni; Jan Siemens; Arnd Heuser; Louise Van Der Weyden; Andreas L. Birkenfeld; Thoralf Niendorf; James F.A. Poulet; Tamas L. Horvath; Matthias H. Tschöp; Matthias Heinig; Mirko Trajkovski; Volker Haucke; Matthew N. Poy

doi:10.1038/nn.4590

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

Thomas Rathjen, Xin Yan, Natalia L. Kononenko, Min Chi Ku, Kun Song, Leiron Ferrarese, Valentina Tarallo, Dmytro Puchkov, Gaga Kochlamazashvili, Sebastian Brachs, Luis Varela, Klara Szigeti-Buck, Chun Xia Yi, Sonja C. Schriever, Sudhir Gopal Tattikota, Anne Sophie Carlo, Mirko Moroni, Jan Siemens, Arnd Heuser, Louise Van Der WeydenAndreas L. Birkenfeld, Thoralf Niendorf, James F.A. Poulet, Tamas L. Horvath, Matthias H. Tschöp, Matthias Heinig, Mirko Trajkovski, Volker Haucke, Matthew N. Poy

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English (US)
Pages (from-to)	1096-1103
Number of pages	8
Journal	Nature neuroscience
Volume	20
Issue number	8
DOIs	https://doi.org/10.1038/nn.4590
State	Published - Aug 1 2017
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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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., ... Poy, M. N. (2017). Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1. Nature neuroscience, 20(8), 1096-1103. https://doi.org/10.1038/nn.4590

Rathjen, T, Yan, X, Kononenko, NL, Ku, MC, Song, K, Ferrarese, L, Tarallo, V, Puchkov, D, Kochlamazashvili, G, Brachs, S, Varela, L, Szigeti-Buck, K, Yi, CX, Schriever, SC, Tattikota, SG, Carlo, AS, Moroni, M, Siemens, J, Heuser, A, Van Der Weyden, L, Birkenfeld, AL, Niendorf, T, Poulet, JFA, Horvath, TL, Tschöp, MH, Heinig, M, Trajkovski, M, Haucke, V & Poy, MN 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

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title = "Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1",

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.",

author = "Thomas Rathjen and Xin Yan and Kononenko, {Natalia L.} and Ku, {Min Chi} and Kun Song and Leiron Ferrarese and Valentina Tarallo and Dmytro Puchkov and Gaga Kochlamazashvili and Sebastian Brachs and Luis Varela and Klara Szigeti-Buck and Yi, {Chun Xia} and Schriever, {Sonja C.} and Tattikota, {Sudhir Gopal} and Carlo, {Anne Sophie} and Mirko Moroni and Jan Siemens and Arnd Heuser and {Van Der Weyden}, Louise and Birkenfeld, {Andreas L.} and Thoralf Niendorf and Poulet, {James F.A.} and Horvath, {Tamas L.} and Tsch{\"o}p, {Matthias H.} and Matthias Heinig and Mirko Trajkovski and Volker Haucke and Poy, {Matthew N.}",

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AU - Kochlamazashvili, Gaga

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AU - Tattikota, Sudhir Gopal

AU - Carlo, Anne Sophie

AU - Moroni, Mirko

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AU - Heuser, Arnd

AU - Van Der Weyden, Louise

AU - Birkenfeld, Andreas L.

AU - Niendorf, Thoralf

AU - Poulet, James F.A.

AU - Horvath, Tamas L.

AU - Tschöp, Matthias H.

AU - Heinig, Matthias

AU - Trajkovski, Mirko

AU - Haucke, Volker

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

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