Xin Yan, Zhen Wang, Vanessa Schmidt, Anton Gauert, Thomas E Willnow, Matthias Heinig, Matthew N Poy
Molecular metabolism 2018 FebObesity 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. 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. 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 Lepob/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. 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. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.
Xin Yan, Zhen Wang, Vanessa Schmidt, Anton Gauert, Thomas E Willnow, Matthias Heinig, Matthew N Poy. Cadm2 regulates body weight and energy homeostasis in mice. Molecular metabolism. 2018 Feb;8:180-188
PMID: 29217450
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