Cadm2 regulates body weight and energy homeostasis in mice

Xin Yan, Zhen Wang, Vanessa Schmidt, Anton Gauert, Thomas E. Willnow, Matthias Heinig, Matthew N. Poy

Research output: Contribution to journalArticlepeer-review

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 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. 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.

Original languageEnglish (US)
Pages (from-to)180-188
Number of pages9
JournalMolecular Metabolism
Volume8
DOIs
StatePublished - Feb 2018
Externally publishedYes

Keywords

  • Cadm2/SynCAM2
  • Energy homeostasis
  • Genome-wide association studies
  • Insulin sensitivity
  • Leptin signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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