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Cadm2 regulates body weight and energy homeostasis in mice

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Item Type:Article
Title:Cadm2 regulates body weight and energy homeostasis in mice
Creators Name:Yan, X., Wang, Z., Schmidt, V., Gauert, A., Willnow, T.E., Heinig, M. and Poy, M.N.
Abstract:OBJECTIVE: Obesity is strongly linked to genes regulating neuronal signaling and function, implicating the central nervous system in the maintenance of body weight and energy metabolism. Genome-wide association studies identified significant associations between body mass index (BMI) and multiple loci near Cell adhesion molecule2 (CADM2), which encodes a mediator of synaptic signaling enriched in the brain. Here we sought to further understand the role of Cadm2 in the pathogenesis of hyperglycemia and weight gain. METHODS: We first analyzed Cadm2 expression in the brain of both human subjects and mouse models and subsequently characterized a loss-of-function mouse model of Cadm2 for alterations in glucose and energy homeostasis. RESULTS: We show that the risk variant rs13078960 associates with increased CADM2 expression in the hypothalamus of human subjects. Increased Cadm2 expression in several brain regions of Lep(ob/ob) mice was ameliorated after leptin treatment. Deletion of Cadm2 in obese mice (Cadm2/ob) resulted in reduced adiposity, systemic glucose levels, and improved insulin sensitivity. Cadm2-deficient mice exhibited increased locomotor activity, energy expenditure rate, and core body temperature identifying Cadm2 as a potent regulator of systemic energy homeostasis. CONCLUSIONS: Together these data illustrate that reducing Cadm2 expression can reverse several traits associated with the metabolic syndrome including obesity, insulin resistance, and impaired glucose homeostasis.
Keywords:Cadm2/SynCAM2, Energy Homeostasis, Insulin Sensitivity, Genome-Wide Association Studies, Leptin Signaling, Animals, Mice
Source:Molecular Metabolism
Page Range:180-188
Date:February 2018
Official Publication:https://doi.org/10.1016/j.molmet.2017.11.010
PubMed:View item in PubMed

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