Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1.
Thomas RathjenXin YanNatalia L KononenkoMin-Chi KuKun SongLeiron FerrareseValentina TaralloDmytro PuchkovGaga KochlamazashviliSebastian BrachsLuis VarelaKlara Szigeti-BuckChun-Xia YiSonja C SchrieverSudhir Gopal TattikotaAnne Sophie CarloMirko MoroniJan SiemensArnd HeuserLouise van der WeydenAndreas L BirkenfeldThoralf NiendorfJames F A PouletTamas L HorvathMatthias H TschöpMatthias HeinigMirko TrajkovskiVolker HauckeMatthew N PoyPublished in: Nature neuroscience (2017)
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.
Keyphrases
- cell adhesion
- weight gain
- weight loss
- poor prognosis
- body weight
- body mass index
- bariatric surgery
- high fat diet induced
- metabolic syndrome
- insulin resistance
- endothelial cells
- birth weight
- type diabetes
- genome wide association
- roux en y gastric bypass
- spinal cord
- long non coding rna
- binding protein
- physical activity
- skeletal muscle
- dna methylation
- transcription factor
- brain injury
- induced pluripotent stem cells
- subarachnoid hemorrhage
- cerebral ischemia
- pluripotent stem cells
- prefrontal cortex
- adipose tissue